The present disclosure relates to field of lyophilized/freeze-dried viral combination composition/formulation and methods for manufacturing and obtaining the composition comprising at least three live attenuated virus selected from a group of Coronavirus, Measles virus and Rubella virus; and stabilizers comprising of at least one carbohydrate, at least one amino acid and at least one hydrolyzed protein. The said lyophilized/freeze-dried viral combination composition/formulation is a vaccine composition that preserves the desired characteristics of each virus, including stability and immunogenicity. The composition can be safely administered subcutaneously as a combination vaccine composition such that the immunogenicity of each of the measles, rubella and SARS-CoV-2 is not inferior to that observed for each of the three viruses when administered as individual vaccines and is found to be equivalent or improved as compared to immunogenicity of SARS-CoV-2 vaccine given intranasally. The purification process is devoid of chromatography steps.
The present disclosure relates to field of lyophilized/freeze-dried viral vaccine composition and methods for manufacturing and obtaining the vaccine composition comprising live attenuated flavivirus as vaccine antigen selected from a group of yellow fever virus, dengue virus, Japanese encephalitis (JE) virus, Kunjin virus, West Nile (WN) virus, tick-borne encephalitis (TBE) virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Zika virus vaccine antigen; and stabilizers comprising sugar or sugar alcohol; amino acids; lactalbumin hydrolysate and gelatin. Post reconstitution, the composition preserves the desired characteristics of the virus, including immunogenicity and stability. The composition of the present disclosure can be safely administered subcutaneously or intramuscularly such that the vaccine composition induces complete immune response to yellow fever virus infectious agent and meets the criterion for the seroprotection for the said immunogenic components comprising yellow fever virus.
The present disclosure relates to vaccine compositions comprising pneumococcal polysaccharide-carrier protein conjugates. The present disclosure particularly relates to improved, stable, immunogenic multivalent Streptococcus pneumoniae polysaccharide-protein conjugate vaccine compositions having at least three distinct carrier proteins, preparing the vaccine compositions and methods for prevention and/or treatment of subjects with Streptococcus pneumoniae. These multivalent pneumococcal compositions will overcome carrier induced epitopic suppression, provide enhanced immune response for new serotypes (as compared to existing approved vaccines) and also help address the emergence of non-vaccine serotypes.
Present invention provides fusion proteins with desired reduction in factor H binding, particularly the present invention provides optimized manufacturing process for fusion proteins and formulations comprising the fusion proteins. Present invention provides an efficient platform process for manufacturing an effective vaccine formulation against Neisseria meningitidis that meets multiple criteria including improved immunogenicity, safety, stability, and affordability.
C07K 14/22 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Neisseriaceae (F), e.g. Acinetobacter
C12N 15/31 - Genes encoding microbial proteins, e.g. enterotoxins
C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
5.
METHOD FOR MANUFACTURING VIRAL VACCINES AND COMPOSITIONS THEREOF
Present invention provides a method of producing clarified virus pool of virus to obtain a lyophilized/freeze-dried live attenuated virus immunogenic composition/ formulation comprising atleast one or more than one antigens/immunogens. Present invention provides a method of producing a clarified virus pool of viruses such as measles, mumps, rubella. It provides the improved large scale affordable /safe manufacturing processes (encompassing cultivation, purification & formulation stages) that utilize minimum animal origin components, provide high virus yield, ensure virus integrity/stability preservation across manufacturing & storage.
A61K 9/19 - Particulate form, e.g. powders lyophilised
6.
METHODS FOR ENHANCING ANTIBODY PRODUCTIVITY IN MAMMALIAN CELL CULTURE AND MINIMIZING AGGREGATION DURING DOWNSTREAM, FORMULATION PROCESSES AND STABLE ANTIBODY FORMULATIONS OBTAINED THEREOF
The invention describes an efficient platform for antibody manufacturing and formulation that provides i) cell culture process with improved feeding strategy resulting in high antibody titer between 2 gm/L to 5 gm/L; ii) improved purification process showing optimal percentage recovery, high purity monomer content, minimum aggregation/particulate formation, minimum impurity levels; and iii) high concentration stable liquid formulation with optimal osmolality and low viscosity across different temperature excursions and devoid of aggregation. The preferred antibodies include IgG1 monoclonal antibody specific to the Dengue virus epitope in domain III of the E protein and IgG1 monoclonal antibody specific to the rabies virus surface G glycoprotein.
Described herein are modified SARS-CoV-2 variants. These viruses have been recoded, for example, codon deoptimized or codon pair bias deoptimized and are useful for reducing the likelihood or severity of a SARS-CoV-2 variant infection, preventing a SARS-CoV-2 variant infection, eliciting and immune response, or treating a SARS-CoV-2 variant infection.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical products for the treatment of cancer; Pharmaceutical preparations for the treatment of infectious diseases; Pharmaceutical preparations for the treatment of viral infections; Pharmaceutical preparations for the treatment of hormonal disorders; Vaccines for human use
9.
METHOD FOR MANUFACTURING RECOMBINANT TRANSFERRIN BINDING PROTEINS AND VACCINE COMPOSITIONS COMRPISING SAME
The present disclosure relates to manufacturing transferrin binding proteins. Specifically, the present disclosure relates to a simple, scalable, commercially viable fermentation and purification process for obtaining recombinant transferrin binding protein (rTbp-B) along with high recovery, low impurity/ aggregate content, and at the same time retains the integrity of the protein. The method uses a single chromatographic step and does not require tagging of proteins as compared to multiple chromatographic steps used previously and still manages to provide r-Tbp-B with at least 95 % purity.
C07K 14/22 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Neisseriaceae (F), e.g. Acinetobacter
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
The present invention relates to an improved process for purification of bacterial capsular polysaccharides, more specifically capsular polysaccharides of gram negative bacteria. The process comprises of concentration and diafiltration of harvest, treatment with anionic detergent and strong alkali followed by centrifugation, diafiltration and cationic detergent based precipitation of bacterial polysaccharides. The process results in significant reduction of endotoxin, protein and nucleic acid impurities thereby providing higher recovery of capsular polysaccharide with the desired O-acetyl levels. Said process is scalable, non-enzymatic, and employs fewer purification steps.
The present invention relates to the construction of Adenovirus-based vectors und to their use for inducing a broad, robust and durable cellular and humoral immune response in a subject.
The present disclosure relates to alternative, cost effective, rapid and simple methods for bacterial capsular polysaccharide (CPS) manufacturing resulting in 1) simultaneous sizing and purification of CPS 2) high CPS yield, 3) improved CPS purity and removal of protein and nucleic acid contaminants, 4) CPS with preserved epitopic conformation and 5) stable and immunogenic polysaccharide-protein conjugate vaccines comprising of said size reduced and purified CPS The method particularly comprises subjecting crude/native bacterial polysaccharide to an oxidizing agent to obtain high purity, high yield and structurally intact CPS having optimal molecular size and other desirable CPS attributes. The method is amenable for commercial scale manufacturing of polysaccharide-protein conjugate vaccines.
The invention relates to the use of a polypeptide derived from the adenylate cyclase of a Bordetella sp. (CyaA-derived polypeptide) by deletion of a segment of at least 93 amino acid residues, in particular a polypeptide derived from CyaA of Bordetella pertussis, as an immunomodifying antigen of the TH1/TH17-oriented immune response in an immunogenic composition. The invention relates to a vaccine candidate comprising such CyaA-derived polypeptide, either in an acellular immunogenic composition for active immunization against a condition causally related to the infection of a host by Bordetella sp. or in a combination composition encompassing said acellular immunogenic composition.
The present disclosure relates to novel immunogenic monovalent and multivalent polysaccharide-protein conjugate vaccine compositions comprising a polysaccharide selected from Salmonella serovar strains S. typhi; S. paratyphi A; S. typhimurium and S. enteritidis and alternative improved methods of polysaccharide fermentation, polysaccharide purification, polysaccharide-protein conjugation and stable formulation. The present disclosure further relates to methods for inducing an immune response in subjects against Salmonella typhi and non-typhi related diseases and/or for reducing or preventing Salmonella typhi and non-typhi related diseases in subjects using the compositions disclosed herein. The vaccine elicits bactericidal antibodies and is useful for prevention of gastroenteritis, enteric and typhoid fever.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
Described herein are modified SARS-CoV-2 coronaviruses. These viruses have been recoded, for example, codon deoptimized or codon pair bias deoptimized and are useful for reducing the likelihood or severity of a SARS-CoV-2 coronavirus infection, preventing a SARS-CoV-2 coronavirus infection, eliciting and immune response, or treating a SARS-CoV-2 coronavirus infection.
: FREEZE-DRIED VIRAL COMBINATION VACCINE COMPOSITIONS AND PROCESS FOR PREPARATION THEREOF The present disclosure relates to field of lyophilized/freeze-dried viral combination composition/formulation and methods for manufacturing and obtaining the composition comprising at least three live attenuated virus selected from a group of Coronavirus, Measles virus and Rubella virus; and stabilizers comprising of at least one carbohydrate, at least one amino acid and at least one hydrolyzed protein. The said lyophilized/freeze-dried viral combination composition/formulation is a vaccine composition that preserves the desired characteristics of each virus, including stability and immunogenicity. The composition can be safely administered subcutaneously as a combination vaccine composition such that the immunogenicity of each of the measles, rubella and SARS-CoV-2 is not inferior to that observed for each of the three viruses when administered as individual vaccines and is found to be equivalent or improved as compared to immunogenicity of SARS-CoV-2 vaccine given intranasally. The purification process is devoid of chromatography steps.
The present disclosure provides a process for assaying stability of monovalent and/or multivalent, liquid and lyophilized polysaccharide protein conjugate vaccine compositions using HPLC-SEC method. The method provides stability analysis (lot to lot) of polysaccharide protein conjugate vaccine with respect to aggregation profile, molar mass distribution and/or molecular size distribution, and data can be utilized for quality control during storage and batch release. The method is performed in the presence of multiple carrier proteins, free polysaccharides and excipient, without any interference of said components.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
The present disclosure relates to immunogenic compositions comprising tetanus, diphtheria, and acellular pertussis (Tdap) antigens, and a toll-like receptor 9 (TLR9) agonist, such as oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions may further comprise an aluminum salt adjuvant to which the Tdap antigens are adsorbed. The immunogenic compositions are suitable for active booster immunization against tetanus, diphtheria, and pertussis in an individual in need thereof.
Described herein are modified SARS-CoV-2 variants. These viruses have been recoded, for example, codon deoptimized or codon pair bias deoptimized and are useful for reducing the likelihood or severity of a SARS-CoV-2 variant infection, preventing a SARS-CoV-2 variant infection, eliciting and immune response, or treating a SARS-CoV-2 variant infection.
The present disclosure provides compositions and methods for manufacturing and obtaining a live attenuated Influenza vaccine (LAIV) composition that can be delivered intranasally to provide protection against influenza virus infection. Said LAIV strains are based on cold adapted, temperature sensitive and attenuated phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of the wild type pandemic or seasonal influenza strains. Also, said LAIV strains are further adapted to grow in MDCK cells (Madin Darby canine kidney cells). The use of eggs is avoided in large scale vaccine manufacturing. The purification process is devoid of chromatography steps. The said LAIV composition includes one or more live attenuated influenza vaccine virus and is devoid of polymers and surfactants.
The present disclosure relates to alternative, cost effective, rapid and simple methods for bacterial capsular polysaccharide (CPS) manufacturing resulting in 1) simultaneous sizing and purification of CPS 2) high CPS yield, 3) improved CPS purity and removal of protein and nucleic acid contaminants, 4) CPS with preserved epitopic conformation and 5) stable and immunogenic polysaccharide-protein conjugate vaccines comprising of said size reduced and purified CPS The method particularly comprises subjecting crude/ native bacterial polysaccharide to an oxidizing agent to obtain high purity, high yield and structurally intact CPS having optimal molecular size and other desirable CPS attributes. The method is amenable for commercial scale manufacturing of polysaccharide-protein conjugate vaccines.
The present disclosure relates to a fully liquid immunogenic composition comprising a combination of antigens/immunogens. The immunogenic composition comprises optimum amount of antigens/immunogens to confer protection against a number of diseases. The composition exhibits improved immunogenicity and stability. A process for preparing the vaccine composition is also disclosed.
The present disclosure relates to immunogenic compositions comprising tetanus, diphtheria, and acellular pertussis (Tdap) antigens, and a toll-like receptor 9 (TLR9) agonist, such as oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions may further comprise an aluminum salt adjuvant to which the Tdap antigens are adsorbed. The immunogenic compositions are suitable for active booster immunization against tetanus, diphtheria, and pertussis in an individual in need thereof.
The present disclosure relates to immunogenic compositions comprising tetanus, diphtheria, and acellular pertussis (Tdap) antigens, and a toll-like receptor 9 (TLR9) agonist, such as oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions may further comprise an aluminum salt adjuvant to which the Tdap antigens are adsorbed. The immunogenic compositions are suitable for active booster immunization against tetanus, diphtheria, and pertussis in an individual in need thereof.
Described herein are modified SARS-CoV-2 coronaviruses. These viruses have been recoded, for example, codon deoptimized or codon pair bias deoptimized and are useful for reducing the likelihood or severity of a SARS-CoV-2 coronavirus infection, preventing a SARS-CoV-2 coronavirus infection, eliciting and immune response, or treating a SARS-CoV-2 coronavirus infection.
Stable lyophilized immunogenic compositions include inter alia live attenuated recombinant flaviviruses, more preferably live attenuated recombinant dengue viruses, at least one carbohydrate, at least one amino acid and is particularly amenable to rapid freeze-drying treatments wherein, the composition preserves desired characteristics of a virus, including virus viability, immunogenicity and stability. The immunogenic composition is devoid of preservatives, polymers and surfactants. The methods for manufacturing the stable lyophilized immunogenic compositions are also provided.
The present disclosure relates to novel immunogenic monovalent and multivalent polysaccharide-protein conjugate vaccine compositions comprising a polysaccharide selected from Salmonella serovar strains S. typhi; S. paratyphi A; S. typhimurium and S. enteritidis and alternative improved methods of polysaccharide fermentation, polysaccharide purification, polysaccharide-protein conjugation and stable formulation. The present disclosure further relates to methods for inducing an immune response in subjects against Salmonella typhi and non-typhi related diseases and/or for reducing or preventing Salmonella typhi and non-typhi related diseases in subjects using the compositions disclosed herein. The vaccine elicits bactericidal antibodies and is useful for prevention of gastroenteritis, enteric and typhoid fever.
The present disclosure relates to a method for obtaining purified bacterial polysaccharides. The method comprises simultaneous removal of impurities as well as sizing of bacterial polysaccharides using an acid instead of conventional mechanical sizing methods. The method is simple, rapid and cost effective. The method results in high polysaccharide recovery and low impurity content. The purified polysaccharide obtained by the method of the present disclosure may be used for large scale production of polysaccharide-protein conjugate vaccines.
C08B 37/00 - Preparation of polysaccharides not provided for in groups Derivatives thereof
C12P 1/04 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymesGeneral processes for the preparation of compounds or compositions by using microorganisms or enzymes by using bacteria
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
B01D 21/26 - Separation of sediment aided by centrifugal force
42.
IMMUNOGENIC COMPOSITIONS AGAINST ENTERIC DISEASES AND METHODS FOR ITS PREPARATION THEREOF
SalmonellaS. typhi; S. paratyphi AS. typhimurium and S. enteritidisSalmonella typhiSalmonella typhiSalmonella typhi and non-typhi related diseases in subjects using the compositions disclosed herein. The vaccine elicits bactericidal antibodies and is useful for prevention of gastroenteritis, enteric and typhoid fever.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Medicinal and pharmaceutical preparations, namely, anti-infective preparations, antiviral preparations, antibiotics, antitoxins, antifungal preparations, and vaccines; Pharmaceutical preparations and substances for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmic, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric, and immune system related diseases and disorders; Dietary and nutritional supplements
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Medicinal and pharmaceutical preparations, namely, human vaccine preparations, anti-toxins in the nature of tetanus vaccines, antivenom, vaccines against Diphtheria, Tetanus and Pertussis, vaccines against measles, mumps and rubella, vaccines against Hepatitis B, vaccines against polio, vaccines against pneumococcal infections, tuberculosis, and influenza, vaccines against coronavirus, vaccines against human papillomavirus, vaccines against rabies, vaccines against monkey pox, pharmaceutical preparations and substances for the treatment of gastrointestinal diseases and disorders, pharmaceutical preparations for the treatment of hormonal disorders, namely, infertility, hyperprolactinemia, pharmaceutical preparations for the treatment of gynaecological diseases and disorders, namely, premenstrual syndrome, menstrual pain, premenstrual tension, endometriosis, menorrhagia, gynaecomastia, secondary amenorrhoea, infertility, uterine fibroids, precocious puberty, pharmaceutical preparations for the treatment of benign fibrocystic breast disease, pharmaceutical preparations for the prevention and treatment of iron deficiency and anaemia in humans, pharmaceutical preparations for the treatment of kidney diseases and disorders, pharmaceutical preparations for the treatment of flat urothelial cell carcinoma in situ (CIS) of the bladder, pharmaceutical preparations for the treatment of prostate cancer, pharmaceutical preparations for the treatment of genitourinary and pelvic diseases, disorders and infections, namely, benign prostatic hypertrophy, pharmaceutical preparations for the relief of pain, pharmaceutical preparations for the treatment of arthritis, muscle soreness and sprains, pharmaceutical preparations for the treatment of hepatological related diseases namely hepatitis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, liver fibroids, and cirrhosis, pharmaceutical preparations for the treatment of diabetic neuropathy, diarrhoea medication, pharmaceutical preparations for the prevention of osteoporosis, pharmaceutical preparations for the treatment of osteoporosis, calcium supplements, pharmaceutical preparations for the prevention of nausea and vomiting during pregnancy, pharmaceutical preparations for the treatment of fever, pharmaceutical cold preparations, dietary supplements consisting of vitamins, amino acids, fatty acids, minerals and trace elements, pharmaceutical hormonal preparations, namely, hormone replacement therapy preparations, oral contraceptives, pharmaceutical preparations for the treatment of dermatological diseases and disorders, namely, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infection, dermatitis, skin pigmentation diseases, psoriasis, acne, rosacea, ichthyosis, vitiligo, urticaria, alopecia areata, dermatitis, and eczema.
The present disclosure provides compositions and methods for manufacturing and obtaining a live attenuated Influenza vaccine (LAIV) composition that can be delivered intranasally to provide protection against influenza virus infection. Said LAIV strains are based on cold adapted, temperature sensitive and attenuated phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of the wild type pandemic or seasonal influenza strains. Also, said LAIV strains are further adapted to grow in MDCK cells (Madin Darby canine kidney cells). The use of eggs is avoided in large scale vaccine manufacturing. The purification process is devoid of chromatography steps. The said LAIV composition includes one or more live attenuated influenza vaccine virus and is devoid of polymers and surfactants.
The present disclosure provides compositions and methods for manufacturing and obtaining a live attenuated Influenza vaccine (LAIV) composition that can be delivered intranasally to provide protection against influenza virus infection. Said LAIV strains are based on cold adapted, temperature sensitive and attenuated phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of the wild type pandemic or seasonal influenza strains. Also, said LAIV strains are further adapted to grow in MDCK cells (Madin Darby canine kidney cells). The use of eggs is avoided in large scale vaccine manufacturing. The purification process is devoid of chromatography steps. The said LAIV composition includes one or more live attenuated influenza vaccine virus and is devoid of polymers and surfactants.
The present invention relates to an improved process for purification of bacterial capsular polysaccharides, more specifically capsular polysaccharides of gram negative bacteria. The process comprises of concentration and dia filtration of harvest, treatment with anionic detergent and strong alkali followed by centrifugation, diafiltration and cationic detergent based precipitation of bacterial polysaccharides. The process results in significant reduction of endotoxin, protein and nucleic acid impurities thereby providing higher recovery of capsular polysaccharide with the desired O-acetyl levels. Said process is scalable, non-enzymatic, and employs fewer purification steps.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
59.
IMPROVED METHODS FOR ENHANCING ANTIBODY PRODUCTIVITY IN MAMMALIAN CELL CULTURE AND MINIMIZING AGGREGATION DURING DOWNSTREAM, FORMULATION PROCESSES AND STABLE ANTIBODY FORMULATIONS OBTAINED THEREOF
The invention describes an efficient platform for antibody manufacturing and formulation that provides i) cell culture process with improved feeding strategy resulting in high antibody titer between 2 gm/L to 5 gm/L; ii) improved purification process showing optimal percentage recovery, high purity monomer content, minimum aggregation/particulate formation, minimum impurity levels; and iii) high concentration stable liquid formulation with optimal osmolality and low viscosity across different temperature excursions and devoid of aggregation. The preferred antibodies include IgG1 monoclonal antibody specific to the Dengue virus epitope in domain III of the E protein and IgG1 monoclonal antibody specific to the rabies virus surface G glycoprotein.
The present disclosure relates to a fully liquid immunogenic composition comprising a combination of antigens/immunogens. The immunogenic composition comprises optimum amount of antigens/immunogens to confer protection against a number of diseases. The composition exhibits improved immunogenicity and stability. A process for preparing the vaccine composition is also disclosed.
The present disclosure relates to a fully liquid immunogenic composition comprising a combination of antigens/immunogens. The immunogenic composition comprises optimum amount of antigens/immunogens to confer protection against a number of diseases. The composition exhibits improved immunogenicity and stability. A process for preparing the vaccine composition is also disclosed.
The present invention is directed to improved methods of Enterovirus inactivation by formaldehyde in presence of tromethamine buffer resulting in maximum recovery of D-antigen. Subsequent adsorption of said sIPV on aluminium hydroxide provides significantly dose reduced sIPV compositions.
The United States of America, as Represented by the Secretary, Department of Health and Human Services (USA)
Inventor
Dhere, Rajeev Mhalasakant
Pisal, Sambhaji Shankar
Zade, Jagdish Kamalaji
Sabale, Rajendra Narayan
Kadam, Ravindra Bapurao
Kamble, Abhijeet Sanjeev
Jiang, Baoming
Glass, Roger
Abstract
Stable, immunogenic combination vaccine(s) comprising a mixture of antigens for prevention and prophylaxis of infections caused by Rotavirus, Poliomyelitis virus, Haemophilus influenzae, Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis and Hepatitis B virus. A multivalent combination vaccine comprises i) significantly dose-reduced Salk-IPV or Sabin-IPV (IPV) antigens prepared by methods of formaldehyde inactivation and alum hydroxide adsorption resulting in maximum D-antigen recovery; ii) Injectable heat inactivated Rotavirus antigen(s) providing broad cross-protective immunity among human rotavirus strains; iii) Hib PRP-carrier protein conjugate having improved stability and immunogenicity; iv) whole cell pertussis antigen with improved immunogenicity and stability; and v) Homogenous fractions of Diphtheria and Tetanus toxoids. Such stable and immunogenic vaccine compositions are made by i) individually adsorbing dose reduced IPV, IRV antigens on alum hydroxide and keeping other antigen(s) unadsorbed or adsorbed on alum phosphate, alum hydroxide, or a combination thereof; and ii) using an order of addition of antigens during blending.
Stable lyophilized immunogenic compositions comprising inter alia live attenuated recombinant flaviviruses, more preferably live attenuated recombinant dengue viruses, at least one carbohydrate, at least one amino acid and is particularly amenable to rapid freeze-drying treatments wherein, the composition preserves desired characteristics of a virus, including virus viability, immunogenicity and stability. The said immunogenic composition is devoid of preservatives, polymers and surfactants. The methods for manufacturing said stable lyophilized immunogenic compositions.
Stable lyophilized immunogenic compositions comprising inter alia live attenuated recombinant flaviviruses, more preferably live attenuated recombinant dengue viruses, at least one carbohydrate, at least one amino acid and is particularly amenable to rapid freeze-drying treatments wherein, the composition preserves desired characteristics of a virus, including virus viability, immunogenicity and stability. The said immunogenic composition is devoid of preservatives, polymers and surfactants. The methods for manufacturing said stable lyophilized immunogenic compositions.
An immunogenic composition comprising of Diphtheria toxoid antigen (D), tetanus toxoid (T) antigen, Hepatitis B surface antigen (HBsAg), inactivated whole-cell B. pertussis (wP) antigen, Haemophilus influenzae type B (Hib) capsular saccharide conjugated to a carrier protein, Inactivated Polio Virus (IPV) antigen and additionally one or more antigens and the method of preparing the same. A fully liquid combination vaccine, showing improved immunogenicity, reduced reactogenicity and improved stability. Improved methods of formaldehyde inactivation, improved adsorption profile of Diphtheria toxoid antigen (D), tetanus toxoid (T) antigen and Hepatitis B (HepB) surface antigen adsorbed individually onto aluminium phosphate adjuvant, minimum total aluminum content (AI3+) and optimized concentration of 2-phenoxyethanol (2-PE) as preservative.
The present invention relates to an improved process for purification of bacterial capsular polysaccharides, more specifically capsular polysaccharides of gram negative bacteria. The process comprises of concentration and dia filtration of harvest, treatment with anionic detergent and strong alkali followed by centrifugation, diafiltration and cationic detergent based precipitation of bacterial polysaccharides. The process results in significant reduction of endotoxin, protein and nucleic acid impurities thereby providing higher recovery of capsular polysaccharide with the desired O-acetyl levels. Said process is scalable, non-enzymatic, and employs fewer purification steps.
The present invention relates to an improved process for purification of bacterial capsular polysaccharides, more specifically capsular polysaccharides of gram negative bacteria. The process comprises of concentration and dia filtration of harvest, treatment with anionic detergent and strong alkali followed by centrifugation, diafiltration and cationic detergent based precipitation of bacterial polysaccharides. The process results in significant reduction of endotoxin, protein and nucleic acid impurities thereby providing higher recovery of capsular polysaccharide with the desired O-acetyl levels. Said process is scalable, non-enzymatic, and employs fewer purification steps.
The invention relates to the use of a polypeptide derived from the adenylate cyclase of a Bordetella sp. (CyaA-derived polypeptide) by deletion of a segment of at least 93 amino acid residues, in particular a polypeptide derived from CyaA of Bordetella pertussis, as an immunomodifying antigen of the TH1/TH17-oriented immune response in an immunogenic composition. The invention relates to a vaccine candidate comprising such CyaA-derived polypeptide, either in an acellular immunogenic composition for active immunization against a condition causally related to the infection of a host by Bordetella sp. or in a combination composition encompassing said acellular immunogenic composition.
The invention relates to the use of a polypeptide derived from the adenylate cyclase of a Bordetella sp. (CyaA-derived polypeptide) by deletion of a segment of at least 93 amino acid residues, in particular a polypeptide derived from CyaA of Bordetella pertussis, as an immunomodifying antigen of the TH1/TH17-oriented immune response in an immunogenic composition. The invention relates to a vaccine candidate comprising such CyaA-derived polypeptide, either in an acellular immunogenic composition for active immunization against a condition causally related to the infection of a host by Bordetella sp. or in a combination composition encompassing said acellular immunogenic composition.
A61K 39/10 - BrucellaBordetella, e.g. Bordetella pertussis
72.
IMPROVED METHODS FOR ENHANCING ANTIBODY PRODUCTIVITY IN MAMMALIAN CELL CULTURE AND MINIMIZING AGGREGATION DURING DOWNSTREAM, FORMULATION PROCESSES AND STABLE ANTIBODY FORMULATIONSOBTAINED THEREOF
The invention, describes an efficient platform for antibody manufacturing and formulation, that provides i) cell culture process with improved feeding strategy resulting in high antibody titer between 2 gm/L to 5 gm/L; ii) improved purification process showing optimal percentage recovery, high purity monomer content, minimum aggregation/particulate formation, minimum impurity levels; and iii) high concentration stable liquid formulation with optimal osmolality and low viscosity across different temperature excursions and devoid of aggregation. The preferred antibodies include lgG1 monoclonal antibody specific to the Dengue virus epitope in domain III of the E protein and lgG1 monoclonal antibody specific to the rabies virus surface G glycoprotein.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
73.
IMPROVED METHODS FOR ENHANCING ANTIBODY PRODUCTIVITY IN MAMMALIAN CELL CULTURE AND MINIMIZING AGGREGATION DURING DOWNSTREAM, FORMULATION PROCESSES AND STABLE ANTIBODY FORMULATIONS OBTAINED THEREOF
The invention, describes an efficient platform for antibody manufacturing and formulation, that provides i) cell culture process with improved feeding strategy resulting in high antibody titer between 2 gm/L to 5 gm/L; ii) improved purification process showing optimal percentage recovery, high purity monomer content, minimum aggregation/particulate formation, minimum impurity levels; and iii) high concentration stable liquid formulation with optimal osmolality and low viscosity across different temperature excursions and devoid of aggregation. The preferred antibodies include lgG1 monoclonal antibody specific to the Dengue virus epitope in domain III of the E protein and lgG1 monoclonal antibody specific to the rabies virus surface G glycoprotein.
The present invention provides methods for preparation of stable multivalent pneumococcal polysaccharide-protein conjugate vaccine formulations. Instant stable formulations show optimal percent adsorption for each conjugate wherein, aggregation can be prevented by employing i) Individual or separate adsorption for conjugates that otherwise show lower percent adsorption by combined adsorption ii) Histidine-Succinic acid buffer system along with shift in pH from neutral pH to acidic pH iii) a polysaccharide to protein ratio between 0.5 to about 1.4 iv) a six-bladed Rushton type turbine impeller in formulation vessels.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/00 - Medicinal preparations containing antigens or antibodies
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
SERUM INSTITUTE OF INDIA PRIVATE LIMITED (India)
Inventor
Dhere, Rajeev Mhalasakant
Pisal, Sambhaji Shankar
Zade, Jagdish Kamalaji
Sabale, Rajendra Narayan
Kadam, Ravindra Bapurao
Kamble, Abhijeet Sanjeev
Jiang, Baoming
Glass, Roger
Abstract
The present invention relates to stable, immunogenic combination vaccine(s) comprising a mixture of antigens for prevention and prophylaxis of infections caused by Rotavirus, Poliomyelitis virus, Haemophilus influenzae, Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis and Hepatitis B virus. The invention particularly provides a multivalent combination vaccine comprising of i) significantly dose reduced Salk IPV or Sabin IPV (IPV) antigens prepared by utilizing improved methods of formaldehyde inactivation and alum hydroxide adsorption resulting in maximum recovery of D-antigen and ii) Injectable heat inactivated Rotavirus antigen(s) obtained from Rotavirus (CDC-9) strains that provides a broad cross-protective immunity among human rotavirus strains, iii) Hib PRP -carrier protein conjugate having improved stability and immunogenicity wherein said Hib PRP -earner protein conjugate is initially prepared by using novel conjugation process and subsequently blended at low temperature in presence of a stabilizer for minimizing free PRP release iv) whole ceil pertussis antigen with improved immunogenicity and stability obtained by addition of whole cell pertussis antigen at a later stage in a blend thereby minimizing hydrolysis based degradation v) Homogenous fractions of Diphtheria toxoid and Tetanus toxoid obtained by removal of undesirable aggregates by using Gel Permeation chromatography. The process of making such stable and immunogenic vaccine compositions by i) individually adsorbing dose reduced IPV. IRV antigens on alum hydroxide and keeping other antigen(s) unadsorbed or adsorbed on Alum Phosphate, Alum hydroxide, on a combination of Alum hydroxide and Alum phosphate and ii) using a particular order of addition of antigens during blending is also disclosed.
THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC) (USA)
Inventor
Dhere, Rajeev Mhalasakant
Pisal, Sambhaji Shankar
Zade, Jagdish Kamalaji
Sabale, Rajendra Narayan
Kadam, Ravindra Bapurao
Kamble, Abhijeet Sanjeev
Jiang, Baoming
Glass, Roger
Abstract
The present invention relates to stable, immunogenic combination vaccine(s) comprising a mixture of antigens for prevention and prophylaxis of infections caused by Rotavirus, Poliomyelitis virus, Haemophilus influenzae, Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis and Hepatitis B virus. The invention particularly provides a multivalent combination vaccine comprising of i) significantly dose reduced Salk IPV or Sabin IPV (IPV) antigens prepared by utilizing improved methods of formaldehyde inactivation and alum hydroxide adsorption resulting in maximum recovery of D-antigen and ii) Injectable heat inactivated Rotavirus antigen(s) obtained from Rotavirus (CDC-9) strains that provides a broad cross-protective immunity among human rotavirus strains, iii) Hib PRP -carrier protein conjugate having improved stability and immunogenicity wherein said Hib PRP -earner protein conjugate is initially prepared by using novel conjugation process and subsequently blended at low temperature in presence of a stabilizer for minimizing free PRP release iv) whole ceil pertussis antigen with improved immunogenicity and stability obtained by addition of whole cell pertussis antigen at a later stage in a blend thereby minimizing hydrolysis based degradation v) Homogenous fractions of Diphtheria toxoid and Tetanus toxoid obtained by removal of undesirable aggregates by using Gel Permeation chromatography. The process of making such stable and immunogenic vaccine compositions by i) individually adsorbing dose reduced IPV. IRV antigens on alum hydroxide and keeping other antigen(s) unadsorbed or adsorbed on Alum Phosphate, Alum hydroxide, on a combination of Alum hydroxide and Alum phosphate and ii) using a particular order of addition of antigens during blending is also disclosed.
The present invention is directed to improved methods of Enterovirus inactivation by formaldehyde in presence of tromethamine buffer resulting in maximum recovery of D-antigen. Subsequent adsorption of said sIPV on aluminium hydroxide provides significantly dose reduced sIPV compositions.
This invention provides an improved process for manufacturing a Rabies monoclonal antibody (HuMab 17C7) that results in low osmolality, minimum secondary metabolites like ammonia and lactate, enhanced cell growth and productivity, minimum aggregation or degradation of monoclonal antibody during purification, thereby improving potency of monoclonal antibody (HuMab 17C7) as compared to human rabies immunoglobulin (hRIG).
The present invention provides methods for preparation of stable multivalent pneumococcal polysaccharide-protein conjugate vaccine formulations. Instant stable formulations show optimal percent adsorption for each conjugate wherein, aggregation can be prevented by employing i) Individual or separate adsorption for conjugates that otherwise show lower percent adsorption by combined adsorption ii) Histidine-Succinic acid buffer system along with shift in pH from neutral pH to acidic pH iii) a polysaccharide to protein ratio between 0.5 to about 1.4 iv) a six-bladed Rushton type turbine impeller in formulation vessels.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
C07K 14/315 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
80.
METHODS FOR IMPROVING THE ADSORPTION OF POLYSACCHARIDE-PROTEIN CONJUGATES AND MULTIVALENT VACCINE FORMULATION OBTAINED THEREOF.
The present invention provides methods for preparation of stable multivalent pneumococcal polysaccharide-protein conjugate vaccine formulations. Instant stable formulations show optimal percent adsorption for each conjugate wherein, aggregation can be prevented by employing i) Individual or separate adsorption for conjugates that otherwise show lower percent adsorption by combined adsorption ii) Histidine-Succinic acid buffer system along with shift in pH from neutral pH to acidic pH iii) a polysaccharide to protein ratio between 0.5 to about 1.4 iv) a six-bladed Rushton type turbine impeller in formulation vessels.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
C07K 14/315 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
81.
IMPROVED METHODS FOR ENTEROVIRUS INACTIVATION, ADJUVANT ADSORPTION AND DOSE REDUCED VACCINE COMPOSITIONS OBTAINED THEREOF
The present invention is directed to improved methods of Enterovirus inactivation by formaldehyde in presence of tromethamine buffer resulting in maximum recovery of D-antigen. Subsequent adsorption of said sIPV on aluminium hydroxide provides significantly dose reduced sIPV compositions.
The present invention is directed to improved methods of Enterovirus inactivation by formaldehyde in presence of tromethamine buffer resulting in maximum recovery of D-antigen. Subsequent adsorption of said sIPV on aluminium hydroxide provides significantly dose reduced sIPV compositions.
N. meningitidis serogroup X polysaccharide in a multivalent meningococcal polysaccharide-protein conjugate vaccine as well as in a multivalent meningococcal plain polysaccharide vaccine. Said assay employs a polyclonal antibody as capture antibody and a novel monoclonal antibody against serogroup X polysaccharide as detection antibody. Further the assay is rapid, robust and reproducible.
C07K 14/22 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Neisseriaceae (F), e.g. Acinetobacter
C07K 14/33 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Clostridium (G)
The present invention is directed to methods for administering antigenic material to a patient as a vaccine against an infection comprising providing both an antigenic material specific to the desired immunological response desired plus an adjuvant comprised of a peptide of a sequence derived from the sequence of pneumococcal surface adhesin A protein (PsaA). Preferably the peptide comprises a sequences derived from one or more sequences of PsaA that contain the epitope regions or contiguous amino acids of SEQ ID NOs 1 or 2. The invention is also directed to vaccine compositions containing adjuvant of the invention and also adjuvant compositions of the invention.
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C07K 14/315 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
A61K 39/00 - Medicinal preparations containing antigens or antibodies
86.
Activation of polysaccharides via the cyanylating agent, 1-cyanobenzotriazole (1-CBT), in the preparation of polysaccharide/protein conjugate vaccines
This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to proteins either directly or through a spacer. These reagents include 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), 1-cyano-imidazole (1-CI), 1-cyanobenzotriazole (1-CBT), or 2-cyanopyridazine-3(2H)one (2-CPO), or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 39/145 - Orthomyxoviridae, e.g. influenza virus
A61K 39/00 - Medicinal preparations containing antigens or antibodies
87.
Activation of polysaccharides via the cyanylating agent, 2-cyanopyridazine-3(2H)-one (2-CPO), in the preparation of polysaccharide/protein conjugate vaccines
This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to proteins either directly or through a spacer. These reagents include 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), 1-cyano-imidazole (1-CI), 1-cyanobenzotriazole (1-CBT), or 2-cyanopyridazine-3(2H)one (2-CPO), or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to proteins either directly or through a spacer. These reagents include 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), 1-cyano-imidazole (1-CI), 1-cyanobenzotriazole (1-CBT), or 2-cyanopyridazine-3(2H)one (2-CPO), or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The instant invention provides improved culture, fermentation and purification conditions for preparing Neisseria meningitidis polysaccharides. The invention in particular relates to a novel fermentation medium, optimal feed solution addition strategies and an improved purification process devoid of any chromatographic methods for obtaining high yield of Neisseria meningitidis X polysaccharide.
A novel alcohol and CTAB free process for purification of capsular polysaccharides, wherein the C-polysaccharide, protein, nucleic acid content of the purified polysaccharide is substantially reduced The said process is cost efficient and less laborious.
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
C08B 37/00 - Preparation of polysaccharides not provided for in groups Derivatives thereof
The invention provides immunogenic polysaccharide protein conjugates comprising capsular polysaccharides from N. Meningitidis serogroup X and methods for preparation thereof. The present invention relates to N. meningitidis X saccharide-carrier protein conjugates prepared by a conjugation reaction. Accordingly, the instant invention relates to multivalent meningococcal polysaccharide protein conjugate composition comprising capsular saccharide from serogroups X and at least one capsular saccharide from A, C, W135 and Y wherein, i) polysaccharides A C W135 X are sized mechanically whereas polysaccharide Y is sized chemically, ii) all saccharide are conjugated to carrier protein via a linker with a cyanylation conjugation chemistry iii) all saccharide to protein ratios in final conjugates are between 0.2 - 0.6 and iv) at least two different carrier proteins selected from the group consisting of TT, DT and CRM197 are utilized.
The invention relates to optimization of culture conditions that utilizes different feed solutions and feeding strategies for improving capsular polyoses (CP) production.
C12P 19/00 - Preparation of compounds containing saccharide radicals
93.
Activation of polysaccharides via the cyanylating agent, 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), in the preparation of polysaccharide/protein conjugate vaccines
This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to proteins either directly or through a spacer. These reagents include 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), 1-cyano-imidazole (1-CI), 1-cyanobenzotriazole (1-CBT), or 2-cyanopyridazine-3(2H)one (2-CPO), or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A novel alcohol and CTAB free process for purification of capsular polysaccharides, wherein the C-polysaccharide, protein,nucleic acid content of the purified polysaccharide is substantially reduced The said process is cost efficient and less laborious.
This invention is directed to methods for removing, preferably simultaneously and in one step, multiple impurities form crude culture samples, and, in particular, the removal of media components, protein, nucleic acids, lipids, and lipopolysaccharides to ultralow levels. Preferably the purification process comprises: (1) binding of the target substance containing one or more contaminants to a chromatography matrix; (2) washing the bound target substance with one or more buffers containing a synergistic combination of a lyotropic agent or organic solvent, a detergent, and a salt component; and (3) desorbing the target substance from the chromatography matrix, so that the eluate contains ultra low levels of contaminants. The reduction of impurities that can be achieved is preferably 91-99.9% as compared to the amount of impurities in the target substance before purification. The invention is also directed to the targets products that have been so purified.
C08B 37/00 - Preparation of polysaccharides not provided for in groups Derivatives thereof
C12N 1/02 - Separating microorganisms from their culture media
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12P 1/00 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymesGeneral processes for the preparation of compounds or compositions by using microorganisms or enzymes
96.
Simple method for simultaneous removal of multiple impurities from culture supernatants to ultralow levels
This invention is directed to methods for removing, preferably simultaneously and in one step, multiple impurities form crude culture samples, and, in particular, the removal of media components, protein, nucleic acids, lipids, and lipopolysaccharides to ultralow levels. Preferably the purification process comprises: (1) binding of the target substance containing one or more contaminants to a chromatography matrix; (2) washing the bound target substance with one or more buffers containing a synergistic combination of a lyotropic agent or organic solvent, a detergent, and a salt component; and (3) desorbing the target substance from the chromatography matrix, so that the eluate contains ultra low levels of contaminants. The reduction of impurities that can be achieved is preferably 91-99.9% as compared to the amount of impurities in the target substance before purification. The invention is also directed to the targets products that have been so purified.
The present invention provides novel lyophilized rotavirus vaccine formulations and methods of their preparation. The formulations include vaccine stabilizers, resulting in a vaccine formulation with enhanced stability and minimal loss of potency. The rotavirus vaccine formulations comprise an advantageous ratio of a disaccharide (such as sucrose) to an amino acid (such as glycine). The lyophilization results in a virus formulation with 100% virus preservation and residual moisture from about 0.8% to 1.4%.
