The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the tyrosine-protein kinase receptor UFO protein (AXL) that are particularly advantageous for quantifying the AXL protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the AXL protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an AXL peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the ER, PR, and/or Ki67 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the ER, PR, and/or Ki67 proteins. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER, PR, and/or Ki67 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Improved methods for treating lung cancer are provided. Tumor samples from patients are analyzed (i) by DNA sequencing to detect the presence of HER2 mutations and (ii) by mass spectrometric proteomic analysis to determine whether HER2 protein is expressed in the tumor cells. Patients respond to therapy with trastuzumab emtansine (T- DM1) or an equivalent antibody-drug conjugate when unique HER2 protein fragments are detected in the patient's tumor cells that harbor HER2 mutations. Conversely, patients do not respond to T-DM1 therapy when the tumor cells contain HER2 mutations but the unique protein fragments are not detected. Detection of HER3 in the tumor cells is a positive predictor of response to treatment.
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Methods are provided for identifying whether a cancer patient, and especially a gastric cancer patient, will be responsive to treatment with a sequential therapeutic strategy comprising a first administration of the FOLFIRI regimen (irinotecan/5-fluoruracil/folinic acid) followed by a separate sequential administration of the combination of the chemotherapy agents docetaxel and cisplatin (FOLFIRI + docetaxel/cisplatin). Specified TUBB3 and TYMP fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells, and especially gastric cancer tumor cells, that are collected from tumor tissue obtained from a cancer patient and compared to reference levels in order to determine if the cancer patients will positively respond to treatment with the sequential combination treatment of FOLFIRI + docetaxel/cisplatin.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
SRM/MRM assays are used to detect and quantitate proteins involved in the process of initiating, inhibiting, maintaining, and/or otherwise modulating a tumor immune response directly in patient tumor tissue. The assays provide an immune profile of the tissue microenvironment, and may be used as part of improved methods of immune-based treatment using agents that manipulate the cancer immune response together with cancer therapeutic agents.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
Methods are provided for identifying whether a tumor, and especially a colon tumor, will be responsive to treatment with the therapeutic agent temozolomide. A specific MGMT fragment peptide is precisely detected and quantitated by SRM-mass spectrometry directly in colon cancer cells collected from colon tumor tissue obtained from a cancer patient. Comparison to reference levels determines if the cancer patient will respond positively or negatively to treatment with the chemotherapeutic agent temozolomide.
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/483 - Physical analysis of biological material
This disclosure provides ten (10) specific peptides, and particular peptide characteristics, from the cell membrane-bound Her2 protein and a diagnostic assay useful for determining the presence and amount of full length and truncated versions of the full-length Her2 protein in cells derived from formalin fixed paraffin embedded tissue.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
G01N 33/74 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving hormones
Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by SRM/MRM assay. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks. A protein digest is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and a designated protein is quantitated in the digest sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the described peptides. The proteins that can be detected and/or quantitated are CD3D, B7H3, B7-2, STAT1, GBP1, GPNMB, CD27, CD3E, and CD8.
G01N 33/567 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent utilising isolate of tissue or organ as binding agent
A01N 1/00 - Preservation of bodies of humans or animals, or parts thereof
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
H01J 49/26 - Mass spectrometers or separator tubes
9.
Methods of treating lung cancer by predicting responders to cisplatin-pemetrexed combination therapy
Methods are provided for identifying whether a lung tumor will be responsive to treatment with the combination of the therapeutic agents cisplatin and pemetrexed. Specified ERCC1, TS, p16, and FRα fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the combination of cisplatin and pemetrexed therapeutic agents.
The present invention provides methods for treating cancer patients comprising assaying tumor tissue from patients and identifying those patients most likely to respond to treatment with a platinum-based agent, such as cisplatin, in combination with pemetrexed. Methods are provided for identifying those lung cancer patients most likely to respond to treatment with the combination of cisplatin + pemetrexed chemotherapy agents ("CDDP+PEM") by determining expression patterns of a set of 38 specific proteins directly in tumor cells derived from patient tumor tissue using SRM mass spectrometry. The method further comprising determining if the patient will respond to treatment with combination therapy, and when proteomic analysis of patient tissue indicates that the patient will respond to treatment with combination therapy, the patient is administered a regimen that includes the pemetrexed/p!atinum agent combination.
Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and a designated protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the described peptides. The proteins that can be detected and/or quantitated are TYMP, TROP2, INSR, and/or the FGFR family of proteins.
G01N 33/74 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving hormones
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
Methods are provided for identifying whether a lung tumor will be responsive to treatment with the combination of the therapeutic agents cisplatin and pemetrexed. Specified ERCC1, TS, p16, and FRα fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the combination of cisplatin and pemetrexed therapeutic agents.
Methods are provided for quantifying CD56 and CHGA proteins directly in formalin- fixed biological samples by Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological samples may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, and FFPE tissue blocks and cells from those blocks. A protein sample may be prepared from said biological sample using the Liquid Tissue reagents and protocol and a designated protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one peptide fragment derived from each of the proteins.
Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by SRM/MRM assay. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks. A protein digest is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and a designated protein is quantitated in the digest sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the described peptides. The proteins that can be detected and/or quantitated are CD3D, B7H3, B7-2, STATl, GBPl, GPNMB, CD27, CD3E, and CD8.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
15.
SRM/MRM ASSAY FOR THE TUBULIN BETA-3 CHAIN (TUBB3) PROTEIN
The current disclosure provides for a specific peptide, and derived ionization characteristics of a peptide from the tubulin beta-3 chain protein (TUBB3) that is particularly advantageous for quantifying the TUBB3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry. A protein sample is prepared from a biological sample using the Liquid Tissue reagents and protocol and the TUBB3 protein is quantitated by SRM/MRM mass spectrometry analysis of the sample, where the specific peptide is quantitated. Methods of treatment are provided in which the measured level of TUBB3 in a patient tumor sample is compared with a reference level and the patient is treated with a taxane-based treatment regimen when the measured TUBB3 level is lower than the reference level. A suitable reference level is, for example, about 700 amol/μg tissue.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Hepatocyte Growth Factor Receptor (Met) protein that are particularly advantageous for quantifying the Met protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Methods also are provided for detecting the presence of the Met (Exl4del) mutant protein.
Methods are provided for determining the diagnosis of whether a liver mass is a benign hepatocellular adenoma or a pre-malignant hepatocellular dysplastic nodule and/or a malignant hepatocellular carcinoma. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in liver mass cells collected from liver mass tissue that was obtained from a patient suffering from the liver mass and compared to reference levels in order to determine if the liver mass is a benign growth or a pre-cancer and/or cancer.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
Methods are provided for identifying whether a tumor will be responsive to treatment with an anti-EGFR agent. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells collected from tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with an anti-EGFR agent such as, for example, pamitumumab and/or erbitux.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Methods of treating breast cancer are provided where a quantitative Her2 assay is used to identify whether a breast tumor will be responsive to treatment with anti-Her2 therapeutic agents such as lapatinib and trastuzumab, followed by selection of a suitable treatment regimen and administration of the regimen. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in breast tumor cells collected from breast tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the breast cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Methods are provided for identifying whether a lung tumor will be responsive to treatment with the therapeutic agents cisplatin and pemetrexed. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the combination of cisplatin and pemetrexed therapeutic agents.
Methods of treating breast cancer are provided where a quantitative Her2 assay is used to identify whether a breast tumor will be responsive to treatment with anti-Her2 therapeutic agents such as lapatinib and trastuzumab, followed by selection of a suitable treatment regimen and administration of the regimen. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in breast tumor cells collected from breast tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the breast cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.
Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and can be tissues and cells treated with formaldehyde containing agents/fixatives including formalin- fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A designated protein is quantitated in the sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. The proteins that can be detected and/or quantitated are TLE3, XRCC1, E- cadherin, PTEN, Vimentin, HGF, MRP1, RFC1, SYP, IDO1, and DHFR.
Methods are provided for treating a gastric cancer patient. A specific Met fragment peptide is precisely quantitated by SRM-mass spectrometry directly in gastric tumor cells collected from gastric tumor tissue that was obtained from the cancer patient and compared to a reference level. If the Met peptide is below the reference level a second therapeutic regimen is used to treat the patient whereas if the Met peptide is above the reference level then a first therapeutic regimen combining, for example, the second regimen with one or more Met inhibitor therapeutic agents may be used to treat the patient.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
Methods are provided for treating a gastric cancer patient. A specific Met fragment peptide is precisely quantitated by SRM-mass spectrometry directly in gastric tumor cells collected from gastric tumor tissue that was obtained from the cancer patient and compared to a reference level. If the Met peptide is below the reference level a second therapeutic regimen is used to treat the patient whereas if the Met peptide is above the reference level then a first therapeutic regimen combining, for example, the second regimen with one or more Met inhibitor therapeutic agents may be used to treat the patient.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/483 - Physical analysis of biological material
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
25.
SRM/MRM assay for the tyrosine-protein kinase receptor UFO (AXL) protein
Peptides from the tyrosine-protein kinase receptor UFO protein (AXL) are provided that are particularly advantageous for quantifying the AXL protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks. A protein digest is prepared from the biological sample and the AXL protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described.
Methods are provided for quantifying the Androgen receptor protein (AR) protein directly in biological samples that have been fixed in formalin, using Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological samples are chemically preserved and fixed and can be, for example, tissues treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks. A protein sample is prepared from said biological sample using, for example, the Liquid Tissue protocol and the AR protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described.
Improved methods are provided for treating cancer patients, particularly patients suffering from lung cancer. Methods are provided for identifying whether a lung tumor will be responsive to treatment with a therapeutic regimen that includes pemetrexed and optionally includes cisplatin. A specific FR-α fragment peptide and a specific GART fragment peptide are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the c therapeutic regimen.
Improved methods are provided for treating cancer patients, particularly patients suffering from lung cancer. Methods are provided for identifying whether a lung tumor will be responsive to treatment with a therapeutic regimen that includes pemetrexed and optionally includes cisplatin. A specific FR-α fragment peptide and a specific GART fragment peptide are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the c therapeutic regimen.
Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol, and the BIM protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
30.
QUANTIFYING HER2 PROTEIN FOR OPTIMAL CANCER THERAPY
Improved methods of treatment are provided for patients suffering from cancer. The methods identify whether a tumor will be responsive to treatment with a therapeutic regime that includes anti-Her2 therapeutic agents. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in tumor cells collected from tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.
The current disclosure provides for specific peptides from the Insulin Receptor Substrate 1 (IRS1) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the IRS1 directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. IRS1 protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an IRS1 peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
32.
SRM/MRM ASSAY FOR THE CYCLIN-DEPENDENT KINASE INHIBITOR 2A (P16) PROTEIN
Methods are provided for quantifying the cyclin-dependent kinase inhibitor 2A protein (p16) p16 protein directly in biological samples that have been fixed in formalin by SRM/MRM mass spectrometry. A protein sample is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and the p16 protein is quantitated in the resulting sample by quantitating in the protein sample at least one fragment peptide from p16. Peptides can be quantitated in modified or unmodified form. An example of a modified form of a p16 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 24/00 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
G01N 33/559 - ImmunoassayBiospecific binding assayMaterials therefor using diffusion or migration of antigen or antibody through a gel, e.g. Ouchterlony technique
33.
Quantifying Her2 protein for optimal cancer therapy
Department of Internal Medicine and Cancer Research, Seoul National University Hospital (Republic of Korea)
Inventor
Bang, Yung-Jue
Hembrough, Todd
An, Eunkyung
Oh, Do-Youn
Abstract
Improved methods of treatment are provided for patients suffering from cancer. The methods identify whether a tumor will be responsive to treatment with a therapeutic regime that includes anti-Her2 therapeutic agents. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in tumor cells collected from tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
34.
SRM/MRM assay for the cyclin-dependent kinase inhibitor 2A (p16) protein
Methods are provided for quantifying the cyclin-dependent kinase inhibitor 2A protein (p16) p16 protein directly in biological samples that have been fixed in formalin by SRM/MRM mass spectrometry. A protein sample is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and the p16 protein is quantitated in the resulting sample by quantitating in the protein sample at least one fragment peptide from p16. Peptides can be quantitated in modified or unmodified form. An example of a modified form of a p16 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Methods are provided for detecting and quantifying the Mesothelin protein (MSLN) in biological samples that have been fixed in formalin using Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological sample may be, for example, tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample and the MSLN protein is quantitated by SRM/MRM mass spectrometry by quantitating one or more MSLN fragment peptides in the protein sample.
The current disclosure provides methods for detecting and quantitating the 6-0- methylguanine-DNA methyltransferase protein (MGMT) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed with formaldehyde containing agents/fixatives and may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and/or paraffin embedded. A protein sample is prepared from the biological sample and the MGMT protein is quantitated in the sample using SRM/MRM mass spectrometry by quantitating one or more fragment peptides.
Methods are provided for quantifying the fibroblast growth factor receptor 2 protein (FGFR2) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological sample may be selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells. A protein sample is prepared from the biological sample and the FGFR2 protein is quantitated in the sample using the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one fragment peptide derived from FGFR2.
The current disclosure provides methods for detecting and quantitating the 6-O-methylguanine-DNA methyltransferase protein (MGMT) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed with formaldehyde containing agents/fixatives and may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and/or paraffin embedded. A protein sample is prepared from the biological sample and the MGMT protein is quantitated in the sample using SRM/MRM mass spectrometry by quantitating one or more fragment peptides.
C07K 2/00 - Peptides of undefined number of amino acidsDerivatives thereof
C07K 4/00 - Peptides having up to 20 amino acids in an undefined or only partially defined sequenceDerivatives thereof
C07K 5/00 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof
C07K 7/00 - Peptides having 5 to 20 amino acids in a fully defined sequenceDerivatives thereof
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 17/00 - Carrier-bound or immobilised peptidesPreparation thereof
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
39.
SRM/MRM assay for the fibroblast growth factor receptor 2 (FGFR2) protein
Methods are provided for quantifying the fibroblast growth factor receptor 2 protein (FGFR2) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological sample may be selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells. A protein sample is prepared from the biological sample and the FGFR2 protein is quantitated in the sample using the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one fragment peptide derived from FGFR2.
The current disclosure provides methods for quantifying the MSLN protein directly in biological samples, including samples that have been fixed in formalin by Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Samples that can be assayed include tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. Methods to prepare a protein sample from such a biological sample are provided and MSLN protein is quantitated by SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins that are particularly advantageous for quantifying the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a KRT5, KRT7, NapsinA, TTF1, TP63, and MUC1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides, and derived ionization characteristics of those peptides from Death Receptor 5 (DR5) protein are provided that are particularly advantageous for quantifying the DR5 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the DR5 protein are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the DR5 protein. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of a DR5 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the ER, PR, and/or Ki67 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the ER, PR, and/or Ki67 proteins. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER, PR, and/or Ki67 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the FASN protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an FASN peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C07K 2/00 - Peptides of undefined number of amino acidsDerivatives thereof
C07K 4/00 - Peptides having up to 20 amino acids in an undefined or only partially defined sequenceDerivatives thereof
C07K 5/00 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof
C07K 7/00 - Peptides having 5 to 20 amino acids in a fully defined sequenceDerivatives thereof
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 17/00 - Carrier-bound or immobilised peptidesPreparation thereof
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
Specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor protein (IR), and its isoforms IR-A and IR-B, that are particularly advantageous for quantifying the IR protein, IR-A isoform and/or IR-B isoform, directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IR protein, and IR-A and/or IR-B isoforms, is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 33/74 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving hormones
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/26 - Mass spectrometers or separator tubes
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins that are particularly advantageous for quantifying the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a KRT5, KRT7, NapsinA, TTF1, TP63, and MUC1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the GTPase KRas Protein (KRas) that are particulariy advantageous for quantifying the KRas protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells,
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the tumor necrosis factor receptor super family member 8 protein (CD30) that are particularly advantageous for quantifying the CD30 protein directly in biological samples that 5 have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Serine/Threoninc-Protein Kinase B-raf (BRAF) that are particularly advantageous for quantifying the BRAF protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
Quantitative analysis of proteins that are targets of chemotherapy by Selected reaction monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry, by measuring modified forms of disclosed specific peptides from the ENT1, ERCC1, FOLR1, RRM1, TUBB3, TOP01, and/or TOP02A proteins. These peptides can be quantified if a modified form thereof comprises a phosphorylated, tyrosine, threonine, serine, and/or other amino acid residues within their amino acid sequence. Biological samples that have been fixed in formalin are used for the analysis.
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods
H01J 49/00 - Particle spectrometers or separator tubes
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins that are particularly advantageous for quantifying the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins directly in biological samples that have been fixed in formalin by the methods of Selected Reaction Monitoring (SRM) mass spectrometry, or as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol and the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry, by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an ALK, Ros, Ron, Ret, TS, and/or FGFR1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3 , that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the Her3 protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a Her3 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Androgen receptor protein (AR) that are particularly advantageous for quantifying the AR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the AR protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an AR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the tyrosine-protein kinase receptor UFO protein (AXL) that are particularly advantageous for quantifying the AXL protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the AXL protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an AXL peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the PD-L1 protein that are particularly advantageous for quantifying the PD-L1 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins that are particularly advantageous for quantifying the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a KRT5, KRT7, NapsinA, TTF1, TP63, and MUC1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides, and derived ionization characteristics of the peptides, from the Ephrin Type-A Receptor 2 (EPHA2) protein are provided that are particularly advantageous for quantifying the EPHA2 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the EPHA2 protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an EPHA2 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
Specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor protein (IR), and its isoforms IR-A and IR-B, that are particularly advantageous for quantifying the IR protein, IR-A isoform and/or IR-B isoform, directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IR protein, and IR-A and/or IR-B isoforms, is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 33/74 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving hormones
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/26 - Mass spectrometers or separator tubes
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the ALK, Ros, Ron, Ret, TS, and/or FGFRI proteins that are particularly advantageous for quantifying the ALK, Ros, Ron, Ret, TS, and/or FGFRI proteins directly in biological samples that have been fixed in formalin by the methods of Selected Reaction Monitoring (SRM) mass spectrometry, or as Multiple Reaction Monitoring (MRM) mass spectrometry.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
60.
SRM/MRM assay for the receptor tyrosine-protein kinase erbB-4 protein (HER4)
Specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-4 Protein (HER4) protein are provided that are particularly advantageous for quantifying the HER4 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol and the HER4 protein is quantitated in the Liquid Tissue™ sample by SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an HER4 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the FASN protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an FASN peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
A01N 25/00 - Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of applicationSubstances for reducing the noxious effect of the active ingredients to organisms other than pests
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
Specific peptides, and derived ionization characteristics of those peptides from Death Receptor 5 (DR5) protein are provided that are particularly advantageous for quantifying the DR5 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the DR5 protein are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the DR5 protein. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of a DR5 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the ER, PR, and/or Ki67 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the ER, PR, and/or Ki67 proteins. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER, PR, and/or Ki67 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides are provided, and derived ionization characteristics of those peptides, from the Hepatocyte Growth Factor Receptor (cMET) protein. The peptides are particularly and surprisingly advantageous for quantifying by the method of Selected Reaction Monitoring (SRM) mass spectrometry the cMET protein directly in biological samples that have been fixed in formalin, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including: formalin-fixed tissue/cells; formalin-fixed/paraffin embedded (FFPE) tissue/cells; FFPE tissue blocks and cells from those blocks; and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol and the cMET protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a cMET peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRTS, KRT7, NapsinA, TTFI, TP63, and/or MUCI proteins that are particularly advantageous for quantifying the KRTS, KRT7, NapsinA, TTFI, TP63, and/or MUCI proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological' samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol, and the BIM protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
This disclosure provides ten (10) specific peptides, and particular peptide characteristics, from the cell membrane-bound Her2 protein and a diagnostic assay useful for determining the presence and amount of full length and truncated versions of the full-length Her2 protein in cells derived from formalin fixed paraffin embedded tissue.
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3, that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the Her3 protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a Her3 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Provided are methods for quantifying the IR protein, IR-A isoform and/or IR-B isoform, directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or Multiple Reaction Monitoring (MRM) mass spectrometry. Biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives. Protein samples are prepared using the Liquid Tissue reagents and protocol and the IR protein, and IR-A and/or IR-B isoforms, are quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
H01J 49/26 - Mass spectrometers or separator tubes
G01T 1/38 - Particle discrimination and measurement of relative mass, e.g. by measurement of loss of energy with distance (dE/dx)
G01N 24/00 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
Objective quantitation of the c-Src protein directly in cancer patient tissue can aid in determining the aggressiveness of an individual patient's tumor as well as help make more informed decisions about choice of therapy. However, the c-Src protein is currently analyzed directly in formalin fixed patient tissue only by immunohistochemistry methodology which is at best subjectively semi-quantitative. This invention describes an objective quantitative assay for the c-Src protein using mass spectrometry as the analytical methodology. Specific peptides, experimentally discovered characteristics about the peptides, and experimentally established assay conditions based on those peptide characteristics are provided for use in a mass spectrometry-based Selected Reaction Monitoring (SRM) assay in order to measure relative or absolute quantitative levels of c-Src directly in a protein preparation obtained from a formalin fixed cancer patient tissue sample.
G01N 24/00 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
71.
SRM/MRM ASSAY FOR THE RECEPTOR TYROSINE-PROTEIN KINASE ERBB-4 PROTEIN (HER4)
Peptides derived from erbB-4 (HER4) are quantified in biological samples that have been fixed in formalin by Selected Reaction Monitoring mass spectrometry.
Peptides, and derived ionization characteristics of the peptides, from the Ephrin Type-A Receptor 2 (EPHA2) protein are provided and are used for quantifying the EPHA2 protein in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or Multiple Reaction Monitoring (MRM) mass spectrometry. The samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin- fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, and FFPE tissue blocks. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocols and the EPHA2 protein is quantitated in a modified or unmodified form by the method of SRM/MRM mass spectrometry. An example of a modified form of an EPHA2 peptide is phosphorylation of a tyrosine, threonine, or serine within the peptide sequence.
Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry or Multiple Reaction Monitoring (MRM) mass spectrometry.
G01N 24/00 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER) proteins that are particularly advantageous for quantifying the ER proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring / Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides, and derived ionization characteristics of those peptides from Death Receptor 5 (DR5) protein are provided that are particularly advantageous for quantifying the DR5 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring / Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the DR5 protein are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the DR5 protein. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of a DR5 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence
The current disclosure provides for specific peptides from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the SPARC directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. SPARC protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an SPARC peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
77.
Methods for measuring the level of insulin-like growth factor 1 receptor (IGF1R) protein using SRM/MRM assay
Peptides from the Insulin-Like Growth Factor 1 Receptor (IGF-1R) protein are provided that are particularly advantageous for quantifying the IGF-1 R protein directly in biological samples, such as samples fixed in formalin. The ionization characteristics of the peptides also are disclosed. The peptides may be used in Selected Reaction Monitoring (SRM) mass spectrometry methods, also referred to Multiple Reaction Monitoring (MRM) mass spectrometry methods. The samples are chemically preserved and fixed, such as tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample may be prepared from the biological sample and the IGF-IR protein is quantitated by the method of SRM/MRM mass spectrometry by quantitating one or more of the described peptides. These peptides can be quantitated in either modified or unmodified form. An example of a modified form of an IGF-1 R peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
78.
Insulin receptor substrate 1 (IRS1) protein SRM/MRM assay
The current disclosure provides for specific peptides from the Insulin Receptor Substrate 1 (IRS1) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying IRS1 directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. IRS1 protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of IRS1 peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Provided are methods for quantifying the Bcl-2-like protein 11 (BIM) protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry or Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed, including tissues or tissue culture cells that have been formalin fixed and or paraffin embedded. A fragmented peptide sample is prepared and quantitated by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Specific peptides are provided, and derived ionization characteristics of those peptides, from the Hepatocyte Growth Factor Receptor (cMET) protein. The peptides are advantageous for quantifying, by the method of Selected Reaction Monitoring (SRM) mass spectrometry, the cMET protein directly in biological samples that have been fixed in formalin, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including: formalin-fixed tissue/cells; formalinfixed/ paraffin embedded (FFPE) tissue/cells; FFPE tissue blocks and cells from those blocks; and tissue culture cells that have been formalin fixed and or paraffin embedded.
This patent application discloses and describes proteins found to be differentially expressed between primary tumor breast cancer cells that did not give rise to recurrent breast cancer disease after initial diagnosis and primary breast cancer cells that did give rise to recurrent breast cancer disease after initial diagnosis. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from breast cancer patients to indicate the likelihood that a breast cancer patient's cancer will recur after initial diagnosis and treatment. Determination of differential expression of these proteins can also be useful for indicating additional therapies to combat the likelihood of recurrent breast cancer. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein the differentially expressed proteins that arc used as diagnostic and prognostic indicators can also be used as targets for therapeutic intervention of breast cancer. Also disclosed and described herein are isotope labeled versions of peptides from the proteins.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3. that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
This patent application discloses and describes proteins found to be differentially expressed between primary tumor breast cancer cells histologicaly defined as early stage (stage 0) breast cancer and primary breast cancer cells histologicaly defined as late stage (stage 3) breast cancer. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from breast cancer patients to indicate the that a breast cancer patient's cancer is in an early, non- aggressive stage or in a late, aggressive stage. Determination of differential expression of these proteins can also be useful for indicating additional therapies to combat the aggressiveness of late stage breast cancer. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein the differentially expressed proteins that are used as diagnostic and prognostic indicators can also be used as targets for therapeutic intervention of breast cancer. Also disclosed and described herein are isotope labeled versions of peptides from the proteins.
This disclosure provides ten (10) specific peptides, and particular peptide characteristics, from the cell membrane-bound Her2 protein and a diagnostic assay useful for determining the presence and amount of full length and truncated versions of the full-length Her2 protein in cells derived from formalin fixed paraffin embedded tissue.
Objective quantitation of the c-Src protein directly in cancer patient tissue can aid in determining die aggressiveness of an individual patient's tumor as well as help make more informed decisions about choice of therapy. However, fee c-Src protein is currently analyzed directly in formalin fixed patient tissue only by immunohistoehemistry methodology which is at best subjectively semi-quantitative. This invention describes an objective quantitative assay for the c-Sre protein using mass spectrometry as the analytical methodology, Specific peptides, experimentally discovered characteristics about the peptides, and experimentally established assay conditions based on those peptide characteristics are provided for use in a mass speetronieiry-based Selected Reaction Monitoring (SRM) assay in order to measure relative- or absolute quantitative levels of c-Src directly in a protein preparation obtained from a formalin fixed cancer patient tissue sample.
Specific peptides are provided that are derived from subsequences of the urokinase-type plasminogen activator protein and the plasminogen activator inhibitor type-1 protein along with assays that can measure those peptides directly in complex protein lysate samples, including protein lysates prepared from histologicaly-processed formalin fixed tissue. The presence and amount of those peptides in samples from a subject can be associated with disease, including cancer, in a subject and provide information about the diagnostic stage/grade/status of the disease/cancer.
The invention provides methods for multiplex analysis of biological samples of formalin-fixed tissue samples. The invention provides for a method to achieve a multiplexed, multi-staged plurality of Liquid Tissue preparations simultaneously from a single histopathologically processed biological sample, where the protocol for each Liquid Tissue preparation imparts a distinctive set of biochemical effects on biomolecules procured from histopathologically processed biological samples and which when each of the preparations is analyzed can render additive and complementary data about the same histopathologically processed biological sample.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor Substrate 1 (IRS 1 ) protein that are particularly advantageous for quantifying the IRS 1 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IRS 1 protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IRS 1 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Insulin-Like Growth Factor 1 Receptor (IGF- I R) protein that are particularly advantageous for quantifying the IGF-IR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin- fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IGF- I R protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IGF-I R peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein that are particularly advantageous for quantifying the SPARC protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fϊxed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid TissueTM reagents and protocol and the SPARC protein is quantitated in the Liquid TissueTM sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an SPARC peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods
The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Epidermal Growth Factor Receptor (EGFR) protein that are particularly advantageous for quantifying the EGFR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the EGFR protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an EGFR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
This patent application discloses and describes a list of proteins that are found to be differentially expressed between normal endometrial epithelial cells and early stage cancerous endometrial epithelial cells. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from endometrial cancer patients, or individuals suspected on having endometrial cancer. In addition, these proteins are also differentially expressed between normal endometrial epithelial cells and epithelial cells of other types of endometrial disease, and thus such diseases can be diagnosed using assays based on these proteins. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein they are not only differentially expressed for use as diagnostic and prognostic indicators of endometrial cancer and other endometrial diseases, but the same proteins are also targets for therapeutic intervention of endometrial cancer and other endometrial diseases.
The invention provides methods for diagnosing diseases such as cancer and other conditions using biological samples. Liquid Tissue samples prepared from histopathologically prepared tissue obtained from a subject surprisingly can be used to identify and, optionally, to quantify analytes that are diagnostic of the presence of a disease, condition or syndrome in the subject.
The current invention provides a method for directly converting histopathologically processed biological samples, tissues, and cells into a multi-use biomolecule lysate. This method allows for simultaneous extraction, isolation, solubilization, and storage of all biomolecules contained within the histopathologically processed biological sample, thereby forming a representative library of said sample. This multi-use biomolecule lysate is dilutable, soluble, capable of being fractionated, and used in any number of subsequent experiments.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
The invention provides methods for multiplex analysis of biological samples of formalin-fixed tissue samples. The invention provides for a method to achieve a multiplexed, multi-staged plurality of Liquid Tissue preparations simultaneously from a single histopathologically processed biological sample, where the protocol for each Liquid Tissue preparation imparts a distinctive set of biochemical effects on biomolecules procured from histopathologically processed biological samples and which when each of the preparations is analyzed can render additive and complementary data about the same histopathologically processed biological sample.
09 - Scientific and electric apparatus and instruments
Goods & Services
Microscope slides; microscope slide covers; [ microscope slide boxes; ] microscope slides for microdissection, namely, slides for laser microdissection; [ microscope slides for cytological analysis; ] microscope slides for medical purposes; microscope slides for laboratory uses; microscope slides that can be used in chemical analysis, biological analysis or patterning for scientific, laboratory, medical research or clinical use, and where the microscope slides are made of a photon transparent support material consisting of a glass, a salt, and/or a polymer
