Serum Institute of India Private Limited

Serum Institute of India Pvt Ltd.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Rajeev Mhalasakant Dhere

Sambhaji Shankar Pisal

Jagdish Kamalaji Zade

Swapan Kumar Jana

Rajendra Narayan Sabale

Dattatreya Sarma Annamraju

Leena Ravindra Yeolekar

Walmik Karbhari Gaikwad

Baoming Jiang

Roger I Glass

Manish Maheshkumar Gautam

Vinit Kumar

Sham Ramdas Tupe

Sunil Mahor

Ravindra Bapurao Kadam

Sandeep Dinkar Baraskar

Rajeev Mehla

Rohit Bapurav Sonar

Chetan Vilas Joshi

Shashikant Janardan Ghodekar

Adar Cyrus Poonawalla

Venkata Vamsi Krishna Malepati

Cyrus Soli Poonawalla

Prashant Shivaji Jadhav

Roger Glass

Hitesh Kumar Malviya

Chetan Vilasrao Joshi

Yashodhan Dilip Anaspure

Swapnil Prabhakar Narale

Milan Shomenath Ganguly

Abhijeet Sanjeev Kamble

Asha Dinesh Mallya

Parikshit Dharampal Tyagi

Umesh Gorakh Sagar

Venkata Vamsi Malepati

Digamber Chahar Singh

Srinivas Reddy Peddireddy

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.

Methods for simultaneous fragmentation and purification of bacterial polysaccharides

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.

Method for obtaining purified bacterial polysaccharides

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.

Stabilized live attenuated influenza vaccine compositions

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.

Method for removal of impurities from bacterial capsular polysaccharide based preparations

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.

Methods for enterovirus inactivation, adjuvant adsorption and dose reduced vaccine compositions obtained thereof

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.

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.

Stable vaccine compositions comprising inter alia live attenuated recombinant flavivirus and process for preparation thereof

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.

Multivalent vaccine composition

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.

Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof

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%.

Stable, dried rotavirus vaccine, compositions and process for preparation thereof

Growing community of inventors

Pune Maharashtra, India

Rajeev Mhalasakant Dhere