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Vaccine Composition

Abstract: The instant invention provides cost effective and immunogenic IPV formulations.The said formulations contain an adjuvant that ca.n enable 5 to 10 fold dose reduction for inactivated polio virus vaccines.

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Patent Information

Application #
Filing Date
16 December 2009
Publication Number
45/2012
Publication Type
INA
Invention Field
PHARMACEUTICALS
Status
Email
Parent Application
Patent Number
Legal Status
Grant Date
2019-03-22
Renewal Date

Applicants

Serum Institute of India Ltd.
212/2  Off Soli Poonawalla Road  Hadapsar  Pune 411 028 Maharashtra India.

Inventors

1. Jadhav Suresh Sakharam
c/o Serum Institute of India Ltd.  of 212/2  Off Soli Poonawalla Road  Hadapsar  Pune 411 028 Maharashtra India.
2. Gairola Sunil Jagdishprasad
c/o Serum Institute of India Ltd.  of 212/2  Off Soli Poonawalla Road  Hadapsar  Pune 411 028 Maharashtra India.
3. Gautam Manish Maheshkumar
c/o Serum Institute of India Ltd.  of 212/2  Off Soli Poonawalla Road  Hadapsar  Pune 411 028 Maharashtra India.

Specification

FORM 2 THE PATENTS ACT, 1970 COMPLETE SPECIFICATION Section 10 "VACCINE COMPOSITION" Serum Institute of India Ltd., an Indian Company, of 212/2, Off Soli Poonawalla Road, Hadapsar, Pune 411 028 Maharashtra India. The following specification particularly describes the nature of this invention and the manner in which it is to be performed: Field of invention The present invention relates to the field of vaccines for protection against polio type 1, 2 and 3 viruses particular to vaccines containing a reduced dose of inactivated polio virus D antigen in monovalent or multivalent forms with an adjuvant to induce protective immunity against polio. Background Art Inactivated poliovirus vaccines (IPVs) that are currently licensed and in use are based on non attenuated (Salk)polio virus vaccine and virus strains: they are therefore also referred to as wild-type IPV (wtlPV). IPV is delivered by intramuscular (IM) or deep subcutaneous {SC) injection. IPV is currently available either as a non-adjuvanted stand-alone formulation, or in various combinations, including DT-IPV (with diphtheria and tetanus toxoids) and hexavalentDTpHepB- Hib-IPV vaccines {additionally with pertussis, hepatitis B, and Haemophilus influenzae b). The future global demand for IPV following eradication of polioviruses could increase from the current level of 80 million doses to 450 million doses per year. Consequently, approaches to "stretch" supplies of IPV are likely to be required. Additionally, various strategies to make IPV available at more affordable prices needs to be evaluated. Reduced-dose vaccine formulations which provide protection against infection using a lower dose of IPV antigen are desirable in situations where the supply of conventional vaccine is insufficient to meet global needs or where the cost of manufacture of the conventional vaccine prevents the vaccine being sold at a price which is affordable for developing countries. Reduced-dose vaccines to permit antigen sparing for pandemic influenza vaccines are known (see for instance WO 2008/128939 ). Oil in water emulsions .per se are well known in the art, and have been suggested to be useful as adjuvants. (EP 399843; WO 95/17210). The currently acceptable standard dose of polio vaccnes contains D antigens as 40 units of inactivated poliovirus type 1 (Hahoney), 8 units of inactivated poliovirus type 2 (MEF-I) and 32 units of inactivated poliovirus type 3 (Saukett) (e.g. inf anrix-IPVT") . Existing preparations of stand-alone IPV do not contain adjuvant. In combination vaccines it has been reported that aluminum based adjuvant enable 3 to 4 fold reduction in IPV dose,please refer Eighth WHO/UNICEF consultation with OPV/IPV manufacturers and NRAs 30l:h Oct 2009 , Geneva, WHO/HO. The three to 4 fold reduction is predicted to be insufficient for stretching global vaccine supplies and significant reduction in cost of manufacture. Thus there is an urgent need in prior art for strategies to allow significant reduction of doses (more than 5 fold) so as to increase vaccine supplies and reduce the cost of manufacture. Such reduction will make such vaccine affordable to developing countries. The present inventors have surprisingly found that by combining an oil-in-water emulsion as adjuvant with the inactivated polio antigen, reduced doses of IPV can be used to induce an adequate or improved level of protection against polio. Such vaccines carry considerable advantages including the ability to provide more doses of IPV vaccines for the individuals in need thereof. Summary Of The Invention The present invention provides various reduced-dose IPV vaccines comprising antigens (which may only have IPV components or may have IPV components combined with other antigens) and an oil-in-water emulsion. Accordingly, in one aspect the present invention provides an IPV vaccine of the invention comprising inactivated poliovirus type 1 at a dose greater than .1 D- antigen units and less than 10 D-antigen units. In one embodiment, the present invention provides an IPV vaccine of the invention comprising inactivated poliovirus type 3 at a dose of between 1 and 7 D-antigen units . In another embodiment, the present invention provides an IPV vaccine of the invention comprising inactivated poliovirus type 2 at a dose of between 0.2 and 2 D-antigen units. In a further aspect, the present invention provides an IPV vaccine of the invention which is a comprising inactivated poiiovirus type and an oil-in-water emulsion. Also according to the instant invention use of said adjuvant results in reduction of effective dose of inactivated polio virus D antigen by 5,6,7,8,9 or 10 fold Said oil-in-water emulsion of present invention comprises a metabolisable oil, an emulsifying agent, and optionally a tocopherol, such as alpha tocopherol. Definitions: The term "vaccine" is optionally substitutable with the term "immunogenic composition" and vice versa. "D-antigen units" (also referred to as "international-units-" or lu): The D antigenic form of the poiiovirus induces protective neutralising antibodies. D antigen units referred to herein (for instance in the vaccines of the invention} are the measured total D antigen units of each bulk IPV antigen type prior to formulation of the final vaccine which are added in each human dose of formulated vaccine (typically 0.5mL final volume). Reliable methods of measuring D-antigen units are well known in the art and are published, for instance, by the European Pharmacopoeia. For instance, D-antigen units may be measured using the ELISA test as described in Example 1 ("D-antigen quantification by ELISA") below. European Pharmacopoeia provides a test sample (European Pharmacopoeia Biological Reference Preparation - available from Ph. Eur. Secretariat, e.g. Code P 216 0000) for standardization of such methods between manufacturers (Pharmeuropa Special Issue, Bio 96-2) . Thus the D-antigen unit value is well understood in the art. The term "dose" herein is typically one administration of the vaccine of the invention, which is typically one injection. A typical human dose is 0.5mL. Of course various doses may be administered in a vaccine administration schedule. The term "IPV" or a vaccine comprising these components herein is intended to mean inactivated polio virus type 1 (e.g. Mahoney, as preferably used, or Brunhilde as marketed by Statens Serum Institut under the name of DiTeKiPol), type 2 (e.g. MEF-I), or type 3 (e.g. Saukett), or a combination of either two or all three of these types. An example of a full (or standard) dose {40-8-32 D antigen units of IPV types 1, 2 and 3 respectively) Ipv vaccine for the purposes of this invention could be Poliorix® (GSK Biologicals S. A.). Thus, where it is stated herein that fold reduction of a standard dose of IPV is present in a vaccine of the invention, it is meant D-antigen units equating to atleast 5 fold reduction and preferably 10 fold reduction of 40, 8, and/or 32 D-antigen units of IPV types 1, 2 and/or 3 respectively {as measured in each bulk IPV antigen type) are formulated within each dose of said vaccine. The term "component(s) " from a pathogen or "component(s ) affording protection to such a pathogen" within the vaccines of the invention herein is intended to mean one or more antigen(s) from that pathogen. The terms "around" or "approximately" herein are taken to mean +10% of the stated value, but should be in keeping with the context of use. Detailed description The present invention provides a vaccine comprising antigens from poliovirus (IPV) and an oil-in-water emuls ion. The antigens of the invention may comprise of IPV type 1 or IPV type 2 or IPV type 3, or IPV types i and 2, or IPV types 1 and 3, or IPV types 2 and 3, or IPV types 1, 2 and 3. Methods of preparing inactivated poliovirus (IPV) are well known in the art. In one embodiment, IPV should comprise types I, 2 and 3 as is common in the vaccine art, and may be the Salk polio vaccine which is inactivated with formaldehyde (see for example, Sutter et al, 2000, Pediatr. Clin. North Am. 47:287; Zimmerman & Spann 1999, Am Fam Physician 59:113; Salk et al., 1954, Official Monthly Publication of the American Public Health Association 44(5):563; Hennesen, 1981, Develop. Biol. Standard 4/:13 9; Budowsky, 1991, Adv. Virus Res. 39:255). Poliovirus may be grown in cell culture. The cell culture may be a VERO cell line or PMKC, which is a continuous cell line derived from monkey kidney. VERO cells can conveniently be cultured on microcarriers. Culture of the VERO cells before and during viral infection may involve the use of bovine-derived material, such as calf serum, and this material should be obtained from sources which are free from bovine spongiform encephalitis (BSE). Culture may also involve materials such as lactalbumin hydro lysafce. After growth, virions may be purified using techniques such as ultrafiltration, diafiltration, and chromatography. Prior to administration to patients, the viruses must be inactivated, and this can be achieved by treatment with formaldehyde. Viruses may be grown, purified and inactivated individually, and then combined to give a concentrate bulk mixture for ipv vaccine use, Antigens in vaccines of the invention will be present in "immunologically effective amounts" i.e. the administration of that amount to an individual, either in a single dose or as part of a series, is effective for treatment or prevention of disease. Dosage treatment may be a single dose schedule or a multiple dose schedule (e.g. including booster doses). Standard doses of polio vaccines today tend to contain 40 D antigen units of inactivated poliovirus type 1, 8 D antigen units of inactivated poliovirus type 2 and 32 D antigen units of inactivated poliovirus type 3 (e.g. Infanrix-1PV™). However, the present inventors have surprisingly found that by combining the antigens with an oil-in-water emulsion • adjuvant, reduced doses of IPV can be used to obtain a good immune response. In one embodiment, an IPV vaccine dose of the present invention may comprise between 1 and 10 D-antigen units of IPV type 1. In another embodiment, a vaccine dose of the present invention may comprise approximately or exactly one tenth of a standard 40 D-antigen unit dose of IPV type 1. In a further embodiment, the vaccines of the present invention may comprise less than 2 D-antigen units, 0.2-2 D-antigen units (equivalent to 2.5-25% of a standard 8 D-antigen unit dose) or around or exactly 0.8 D-antigen units. of IPV type 2 (equivalent to 10% of a standard 8 D-antigen unit dose). In a further embodiment the vaccines of the present invention may comprise more than 1 and less than 8 D- antigen units, for instance around or exactly 3.2 D-antigen units of IPV type 3. In another embodiment, the vaccine of the present invention may comprise approximately or exactly one tenth of a standard 32 D-antigen unit dose of IPV type 3 (equivalent to approximately 3.2 D-antigen units). Also according to the instant invention use of said adjuvant can result in atleast 10 fold reduction in IPV . antigen dose. In yet another aspect there is provided a method of preparing an immunogenic composition, or a kit, for inducing an improved humoral response, against said polio antigen or antigenic composition in a human, that comprises of (a) a low amount, as herein defined, of polio virus antigen or antigenic preparation thereof and (b) an oil-in-water emulsion adjuvant. Suitably said oil-in-water emulsion comprises a metabolisable oil, an emulsifying agent, and optionally a a tocopherol, such as alpha tocopherol. In another specific embodiment, said oil-in-water emulsion adjuvant comprises at least one metabolisable ' oil in an amount of 0.5% to 20% of the total volume, and has oil droplets of which at least 70% by intensity have diameters of less than 1 urn. In one embodiment the polio antigen and the oil-in-water emulsion adjuvant are contained in the same container. It is referred to as 'one vial approach'. In an alternative embodiment, the polio antigen and the oil-in-water emulsion adjuvant are contained in separate containers or vials or units and admixed shortly before or upon administration into the subject. It is referred to as 'two vials approach' . By way of example, when the vaccine is a 2 components vaccine for a total dose volume of injected dose of 0.5 m], the polio antigen may be presented as a standard polio vaccine containing approximately 40-8-32 D antigen units of IPV types 1, 2 and 3 respectively in one vial (500 µl) (antigen container, such as a vial) and another vial contains the adjuvant (4500 µ1). The contents of the antigen container are mixed with the contents of the adjuvant container. Typically, the polio vaccine is a 0.5 ml injected dose and multidose vials contain a 1 :10 vial mixture prior to first subject. Oil-in-water emulsion adjuvant The adjuvant composition of the invention contains an oil-in-water emulsion adjuvant, suitably said emulsion comprises a metabolisable oil in an amount of 0.5% to 20% of the total volume, and having oil droplets of which at least 70 % by intensity have- diameters of less than 1 urn. In order for any oil in water composition to be suitable for human administration, the oil phase of the emulsion system has to comprise a metabolisable oil. The oil may be any vegetable oil, fish oil, animal oil or synthetic oil, which is not toxic to the recipient and is capable of being transformed by metabolism. Nuts, seeds, and grains are common sources of vegetable oils. Synthetic oils are also part of this invention and can include commercially available oils such as NEOBEE® and others. A particularly suitable metabolisable oil is squalene. Squalene (2, 6, 10, 15, 19, 23-Hexamethyl-2, 6,10,14,18,22-tetracosahexaene) is an' unsaturated oil which is found in large quantities in shark-liver oil, and in lower quantities in olive oil, wheat germ oil, rice bran oil, and yeast, and is a particularly suitable oil for use in this invention. Squalene is a metabolisable oil- by virtue of the fact that it is an intermediate in the biosynthesis of cholesterol (Merck index, 10th Edition, entry no.8619 ) . Oil in water emulsions per se are well known in the art, and have been suggested to be useful as adjuvant compositions (EP 399843; WO 95/17210). Suitably the; metabolisable oil is present in- an amount of 0.5% to 20% {final concentration) of the total volume of the immunogenic composition, suitably an amount of 1.0% to 10% of the total volume, suitably in an amount of 2.0% to 6.0% of the total volume. In a specific embodiment, the metabolisable oil is present in a final amount of about 0.5%, 1%, 3.5% or 5% of the total volume of the immunogenic composition. In another specific embodiment, the metabolisable oil is present in a final amount of 0-5%, 1%, 3.57% or 5% of the total volume of the immunogenic composition. A suitable amount of squalene is about 10.7 rag per vaccine dose, suitably from 10.4 to 11.0 mg per vaccine dose. Suitably the oil-in-water emulsion systems of the present invention have a. small oil droplet size in the sub-micron range. Suitably the droplet sizes will be in the range 120 to 750 nm, suitably sizes from 120 to 600 nrn in diameter. Typically the oil-in water emulsion contains oil droplets of which at least 70% by intensity are less than 500 nm in diameter, in particular at least 80% by intensity are less than 300 nm in diameter, suitably at least 90% by intensity are in the range of 120 to 200 nm in diameter. The oil droplet size, i.e. diameter, according to the present invention is given by intensity. There are several ways of determining the diameter of the oil droplet size by intensity. Intensity is measured by use of a sizing instrument, suitably by dynamic light scattering such as the Malvern zetasizer 4000 or suitably the Malvern Zetasizer 3000HS. A detailed procedure is given in Example II.2. A first possibility is to determine the z average diameter ZAD by dynamic light scattering (PCS-Photon correlation spectroscopy); this method additionally give the polydispersity index (PDI), and both the ZAD and PDI are calculated with the cumulants algorithm. These values do not require the knowledge of the particle refractive index. A second mean is to calculate the diameter of the oil droplet by determining the whole particle size distribution by another algorithm, either the Contin, or NNLS, or the automatic "Malvern" one (the default algorithm provided for by the sizing instrument). Most of the time, as the particle refractive index of a complex composition is unknown, only the intensity distribution is taken into consideration, and if necessary the intensity mean originating from this distribution. The oil in water emulsion according to the invention comprises a tocopherol, such as alpha tocopherol. Suitably alpha-tocopherol or a derivative thereof such as alpha-tocopherol succinate is present. Suitably alpha-tocopherol is present in an amount of between 0.2% and 5.0% (v/v) of the total volume of the immunogenic composition, suitably at an amount of 2.5% (v/v) in a 0.5 ml vaccine dose volume, or 0.5% (v/v) in 0.5 ml vaccine dose volume or 1.7- 1.9% (v/v), suitably 1.8% in 0.7 ml vaccine dose volume. By way of clarification, concentrations given in v/v can be converted into concentration in w/v by applying the following conversion factor: a 5% (v/v) alpha-tocopherol concentration is equivalent to a 4.8% (w/v) alpha-tocopherol concentration. A suitable amount of alpha-tocopherol is about 11.9 mg per vaccine dose, suitably from 11. 6 to .12.2 mg per vaccine dose. The oil in water emulsion comprises an emulsifying agent. The emulsifying agent may be present at an amount of 0.01 to 5.0% by weight of the immunogenic composition (w/w), suitably present at an amount of 0.1 to 2.0% by weight (w/w). Suitable concentration are 0.5 to 1.5% by weight (w/w) of the total composition. The emulsifying agent may suitably be polyoxyethyiene sorbitan monooleate (Tween 80). In a specific embodiment, a 0.5 ml vaccine dose volume contains 1 % (w/w) Tween 80, and a 0.7 ml vaccine dose volume contains 0.71 (w/w) Tween 80. In another specific embodiment the concentration of Tween 80 is 0.2% (w/w). A suitable amount of polysorbate 80 is about 4.9 mg per vaccine dose, suitably from 4.6 to 5.2 mg per vaccine dose. Suitably a vaccine dose comprises alpha-tocopherol in an amount of about 11.9 mg per vaccine dose, squalene in an amount of 10.7 mg per vaccine dose, and polysorbate 80 in an amount of about 4.9 mg per vaccine dose. The oil in water emulsion adjuvant may be utilised with other adjuvants or immuno- stimulants and therefore an important embodiment of the invention is an oil in water formulation comprising squalene or another metabolisable oil, a tocopherol, such as alpha tocopherol, and tween 80. The oil in water emulsion may also contain span 85 and/or Lecithin. Typically the oil in water will comprise from 2 to 10% squalene of the total volume of the immunogenic composition, from 2 to 10% alpha tocopherol and from 0.3 to 3% Tween 80, and may be produced according to the procedure described in WO 95/17210. Suitably the ratio of squalene: alpha tocopherol is equal or less than 1 as this provides a more stable emulsion. Span 85 (polyoxyethylene sorbitan trioleate) may also be present, for example at a level of 1 %. The vaccines of the instant invention can comprise of a monovalent composition comprising a polio virus D antigen or antigenic preparation from atleast one inactivated polio virus type selected from a group consisiting of polio virus type 1, type 2 and type 3. The vaccines of the instant invention can comprise of a multivalent composition comprising a polio virus D antigen or antigenic preparation from atleast 2 or atleast 3 inactivated polio virus types. The said multivalent composition can be selected from a group consisting of a) D antigens as 8 Units of inactivated poliovirus type 1, 1.6 units of inactivated poliovirus type 2 and 6.4 units of inactivated poliovirus type 3 .b) D antigens as 6.6 Units of inactivated poliovirus' type 1, 1.3 units of inactivated poliovirus type 2 and 5.3 units of inactivated poliovirus type 3 .c) D antigens as 5.7 Units of inactivated poliovirus type 1, 1.1 units of inactivated poliovirus type 2 and 4.5 units of inactivated poliovirus type 3 .d) D antigens as 5 Units of inactivated poliovirus type 1, 1 units of inactivated poliovirus type 2 and 4 units of inactivated poliovirus type 3 .e)D antigens as 4.4 Units of inactivated poliovirus type 1, 0.88 units of inactivated poliovirus type 2 and 3.5 units of inactivated poliovirus type 3 or f} D antigens as 4 Units of inactivated poliovirus type 1, 0.8 units of inactivated poliovirus type 2 and 3.2 units of inactivated poliovirus type 3 Vaccines of the invention will typically, in addition to the antigenic and adjuvant components mentioned above, comprise one or more "pharmaceutically acceptable carriers or excipients", which include any excipient that does not Itself induce the production of antibodies harmful to the individual receiving the composition. Suitable excipients are typically large, slowly metabolised macromolecul.es such as proteins, saccharides, poly lactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, sucrose (Pa^letti et ah, 2001, Vaccine, 19:2118), trehalose (WO 00/5636.5), lactose and lipid aggregates (such as oil droplets or liposomes). Such carriers are well known to those of ordinary skill in the art. The vaccines may also contain diluents, such as water, saline, glycerol, etc. Additionally, auxiliary substances, such as wetting or emulsifying agents, pH buffering substances, and the like, may be present. Sterile pyrogen-free, phosphate buffered physiologic saline is a typical carrier. A thorough discussion of pharmaceutically acceptable excipients is available in reference Gennaro, 2000, Remington: The Science arid Practice .of Pharmacy, 20th edition, ISBN:0683306472. Compositions may be presented in vials, or they may be presented in ready filled syringes. The syringes may be supplied with or without needles. A syringe will include a single dose of the composition, whereas a vial may include a single dose or multiple doses (e.g. 2 doses). In one embodiment the dose is for human. In a further embodiment the dose is for an adult, adolescent, toddler, infant or less than one year old human and may be administered by injection. Vaccines of the invention may be packaged in unit dose form or in multiple dose form (e.g. 2 doses). The said multidose composition can be selected from a group consisting of 2 dose,5 dose and 10 dose . For multiple dose forms, vials are preferred to pre-filled syringes. Effective dosage volumes can be routinely established, but a typical human dose of the composition for injection has a volume of 0.5mL. Compositions of the invention may be isotonic with respect to humans. Vaccines of the invention may include an antimicrobial, particularly when packaged in a multiple dose format. Thiomersal should be avoided as this leads to loss of potency of the IPV component. Other antimicrobials may be used, such as 2- phenoxyethanol or parabens {methyl, ethyl, propyl parabens). Any preservative is preferably present at low levels. Preservative may be added exogenously and/or may be a component of the bulk antigens which are mixed to form the composition {e.g. present as a preservative in pertussis antigens). In one embodiment, vaccines of the invention are thiomersal free or substantially thiomersal free. By "thiomersal free" or "substantially thiomersal free" it is meant that there is not enough thiomersal present in the final formulation to negatively impact the potency of the IPV component. Vaccines of the invention may comprise detergent e.g. a TVeen (polysorbate), such as Tween 80. Detergents are generally present at low levels e.g. <0.01%. Vaccines of the invention may include sodium salts (e.g. sodium chloride) to give tonicity. The composition may comprise sodium chloride. In one embodiment, the concentration of sodium chloride in the composition of the invention is in the range of 0.1 to 100 mg/mL (e.g. l-50mg/mL, 2-20mg/mL, 5-15mg/mL) and in a further embodiment the concentration of sodium chloride is 10±2mg/mL NaCl e.g. about 9mg/mL. Vaccines of the invention will generally include a buffer. A phosphate,citrate or histidine buffer is typical. Vaccines of the invention may include free phosphate ions in solution (e.g. by the use of a phosphate buffer) in order to favour non-adsorption of antigens. The concentration of free phosphate ions in the composition of the invention is in one embodiment between 0.1 and 10.0 mM, or in another embodiment between 1 and 5mM, or in a further embodiment about 2.5mM. Polio Potency as measured by seroneutralisation test on rats: For the purposes of the invention, the assay for the IPV quantitative evaluation of the vaccine potency of the IPV containing vaccines of the invention should be carried out using a single dose of vaccine and should be done by determining the ratio of test vaccine geometric mean titre (GMT) to reference vaccine GMT and is reported as the relative response (RR) or relative potency (RP), Reference GMT may be the GMT obtained with any IPV vaccine comprising 40-8-32 D-antigen units of IPV types 1-2-3 respectively, and may be the GMT obtained with the known vaccine Poliorix®. Typically, the RP test is carried out by as follows: The potency of poliovirus Types 1, 2 and 3 is determined on rats by seroneutralisation : Groups of 10 healthy rats (Sprague-Dawley (OFA) or any beforehand validated strain) are inoculated intramuscularly with dilutions (1/1.25; 1/3.125; 1/7.81} of the test samples or reference material in phosphate buffer saline. If necessary, the dilution range may be extended to 4 dilutions by inoculating undiluted vaccine and the three previous mentioned dilutions. Ten rats inoculated with the diluent are used as negative controls. Rats are observed once a week, to detect any abnormal reaction. 2 0 to 22 days after the inoculation, each animal is deeply anesthetized, and bled and the serum is collected to be analysed by seroneutralisation test. For the seroneutralisation test, sera are inactivated by incubation at 56 C for 30 minutes in a water bath. Three dilution series of the sera, one for each polio type, are prepared in microplates using the appropriate dilution medium. Plates are stored at +

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1 2911-MUM-2009-FORM 5(13-12-2010).pdf 2010-12-13
1 2911-MUM-2009-FORM-27 [27-09-2024(online)].pdf 2024-09-27
2 2911-MUM-2009-FORM 2(TITLE PAGE)-(13-12-2010).pdf 2010-12-13
2 2911-MUM-2009-RELEVANT DOCUMENTS [27-09-2023(online)].pdf 2023-09-27
3 2911-MUM-2009-RELEVANT DOCUMENTS [30-09-2022(online)].pdf 2022-09-30
3 2911-mum-2009-form 2(13-12-2010).pdf 2010-12-13
4 2911-MUM-2009-RELEVANT DOCUMENTS [28-09-2021(online)].pdf 2021-09-28
4 2911-MUM-2009-DESCRIPTION(COMPLETE)-(13-12-2010).pdf 2010-12-13
5 2911-MUM-2009-RELEVANT DOCUMENTS [19-03-2020(online)].pdf 2020-03-19
5 2911-MUM-2009-CORRESPONDENCE(13-12-2010).pdf 2010-12-13
6 2911-MUM-2009-IntimationOfGrant22-03-2019.pdf 2019-03-22
6 2911-MUM-2009-CLAIMS(13-12-2010).pdf 2010-12-13
7 2911-MUM-2009-PatentCertificate22-03-2019.pdf 2019-03-22
7 2911-MUM-2009-ABSTRACT(13-12-2010).pdf 2010-12-13
8 2911-MUM-2009-FORM 18(14-11-2011).pdf 2011-11-14
8 2911-MUM-2009-CORRESPONDENCE(21-9-2012).pdf 2018-08-10
9 2911-MUM-2009-CORRESPONDENCE(14-11-2011).pdf 2011-11-14
9 2911-MUM-2009-CORRESPONDENCE(8-2-2010).pdf 2018-08-10
10 2911-MUM-2009-CORRESPONDENCE(IPO)-(FER)-(25-11-2014).pdf 2014-11-25
10 2911-MUM-2009-Correspondence-050115.pdf 2018-08-10
11 2911-MUM-2009-Correspondence-180416.pdf 2018-08-10
11 Examination Report Reply Recieved [16-11-2015(online)].pdf 2015-11-16
12 2911-MUM-2009-Correspondence-211215.pdf 2018-08-10
12 Description(Complete) [16-11-2015(online)].pdf 2015-11-16
13 2911-MUM-2009-FORM 1(8-2-2010).pdf 2018-08-10
13 Correspondence [16-11-2015(online)].pdf 2015-11-16
14 2911-MUM-2009-Form 1-180416.pdf 2018-08-10
14 Claims [16-11-2015(online)].pdf 2015-11-16
15 2911-MUM-2009-Form 2(Title Page)-180416.pdf 2018-08-10
15 2911-MUM-2009-JP DOCUMENT (02-12-2015).pdf 2015-12-02
16 2911-MUM-2009-FORM 3 (02-12-2015).pdf 2015-12-02
16 2911-MUM-2009-FORM 3(21-9-2012).pdf 2018-08-10
17 2911-MUM-2009-HearingNoticeLetter.pdf 2018-08-10
17 2911-MUM-2009-CORRESPONDENCE(02-12-2015).pdf 2015-12-02
18 2911-MUM-2009-OTHERS-050115.pdf 2018-08-10
18 Other Document [05-01-2016(online)].pdf 2016-01-05
19 2911-MUM-2009-OTHERS-180416.pdf 2018-08-10
19 Form 13 [05-01-2016(online)].pdf 2016-01-05
20 2911-MUM-2009-OTHERS-211215.pdf 2018-08-10
20 2911-MUM-2009-PETITION UNDER RULE 137 [14-05-2018(online)].pdf 2018-05-14
21 2911-MUM-2009-POWER OF ATTORNEY(8-2-2010).pdf 2018-08-10
21 2911-MUM-2009-Written submissions and relevant documents (MANDATORY) [13-06-2018(online)].pdf 2018-06-13
22 2911-MUM-2009-Power of Attorney-180416.pdf 2018-08-10
22 Form-3.pdf 2018-08-10
23 2911-MUM-2009_EXAMREPORT.pdf 2018-08-10
23 Form-1.pdf 2018-08-10
24 Form-1.pdf 2018-08-10
24 2911-MUM-2009_EXAMREPORT.pdf 2018-08-10
25 2911-MUM-2009-Power of Attorney-180416.pdf 2018-08-10
25 Form-3.pdf 2018-08-10
26 2911-MUM-2009-POWER OF ATTORNEY(8-2-2010).pdf 2018-08-10
26 2911-MUM-2009-Written submissions and relevant documents (MANDATORY) [13-06-2018(online)].pdf 2018-06-13
27 2911-MUM-2009-OTHERS-211215.pdf 2018-08-10
27 2911-MUM-2009-PETITION UNDER RULE 137 [14-05-2018(online)].pdf 2018-05-14
28 2911-MUM-2009-OTHERS-180416.pdf 2018-08-10
28 Form 13 [05-01-2016(online)].pdf 2016-01-05
29 2911-MUM-2009-OTHERS-050115.pdf 2018-08-10
29 Other Document [05-01-2016(online)].pdf 2016-01-05
30 2911-MUM-2009-CORRESPONDENCE(02-12-2015).pdf 2015-12-02
30 2911-MUM-2009-HearingNoticeLetter.pdf 2018-08-10
31 2911-MUM-2009-FORM 3 (02-12-2015).pdf 2015-12-02
31 2911-MUM-2009-FORM 3(21-9-2012).pdf 2018-08-10
32 2911-MUM-2009-Form 2(Title Page)-180416.pdf 2018-08-10
32 2911-MUM-2009-JP DOCUMENT (02-12-2015).pdf 2015-12-02
33 2911-MUM-2009-Form 1-180416.pdf 2018-08-10
33 Claims [16-11-2015(online)].pdf 2015-11-16
34 2911-MUM-2009-FORM 1(8-2-2010).pdf 2018-08-10
34 Correspondence [16-11-2015(online)].pdf 2015-11-16
35 2911-MUM-2009-Correspondence-211215.pdf 2018-08-10
35 Description(Complete) [16-11-2015(online)].pdf 2015-11-16
36 Examination Report Reply Recieved [16-11-2015(online)].pdf 2015-11-16
36 2911-MUM-2009-Correspondence-180416.pdf 2018-08-10
37 2911-MUM-2009-CORRESPONDENCE(IPO)-(FER)-(25-11-2014).pdf 2014-11-25
37 2911-MUM-2009-Correspondence-050115.pdf 2018-08-10
38 2911-MUM-2009-CORRESPONDENCE(14-11-2011).pdf 2011-11-14
38 2911-MUM-2009-CORRESPONDENCE(8-2-2010).pdf 2018-08-10
39 2911-MUM-2009-CORRESPONDENCE(21-9-2012).pdf 2018-08-10
39 2911-MUM-2009-FORM 18(14-11-2011).pdf 2011-11-14
40 2911-MUM-2009-ABSTRACT(13-12-2010).pdf 2010-12-13
40 2911-MUM-2009-PatentCertificate22-03-2019.pdf 2019-03-22
41 2911-MUM-2009-CLAIMS(13-12-2010).pdf 2010-12-13
41 2911-MUM-2009-IntimationOfGrant22-03-2019.pdf 2019-03-22
42 2911-MUM-2009-RELEVANT DOCUMENTS [19-03-2020(online)].pdf 2020-03-19
42 2911-MUM-2009-CORRESPONDENCE(13-12-2010).pdf 2010-12-13
43 2911-MUM-2009-RELEVANT DOCUMENTS [28-09-2021(online)].pdf 2021-09-28
43 2911-MUM-2009-DESCRIPTION(COMPLETE)-(13-12-2010).pdf 2010-12-13
44 2911-MUM-2009-RELEVANT DOCUMENTS [30-09-2022(online)].pdf 2022-09-30
44 2911-mum-2009-form 2(13-12-2010).pdf 2010-12-13
45 2911-MUM-2009-RELEVANT DOCUMENTS [27-09-2023(online)].pdf 2023-09-27
45 2911-MUM-2009-FORM 2(TITLE PAGE)-(13-12-2010).pdf 2010-12-13
46 2911-MUM-2009-FORM-27 [27-09-2024(online)].pdf 2024-09-27
46 2911-MUM-2009-FORM 5(13-12-2010).pdf 2010-12-13

ERegister / Renewals

3rd: 24 Apr 2019

From 16/12/2011 - To 16/12/2012

4th: 24 Apr 2019

From 16/12/2012 - To 16/12/2013

5th: 24 Apr 2019

From 16/12/2013 - To 16/12/2014

6th: 24 Apr 2019

From 16/12/2014 - To 16/12/2015

7th: 24 Apr 2019

From 16/12/2015 - To 16/12/2016

8th: 24 Apr 2019

From 16/12/2016 - To 16/12/2017

9th: 24 Apr 2019

From 16/12/2017 - To 16/12/2018

10th: 24 Apr 2019

From 16/12/2018 - To 16/12/2019

11th: 24 Apr 2019

From 16/12/2019 - To 16/12/2020

12th: 13 Nov 2020

From 16/12/2020 - To 16/12/2021

13th: 07 Dec 2021

From 16/12/2021 - To 16/12/2022

14th: 07 Dec 2022

From 16/12/2022 - To 16/12/2023

15th: 05 Dec 2023

From 16/12/2023 - To 16/12/2024

16th: 20 Nov 2024

From 16/12/2024 - To 16/12/2025

17th: 20 Nov 2024

From 16/12/2025 - To 16/12/2026

18th: 20 Nov 2024

From 16/12/2026 - To 16/12/2027

19th: 20 Nov 2024

From 16/12/2027 - To 16/12/2028

20th: 20 Nov 2024

From 16/12/2028 - To 16/12/2029