WO2005066333A1 - Stabilizing compositions for recombinant viruses - Google Patents
Stabilizing compositions for recombinant viruses Download PDFInfo
- Publication number
- WO2005066333A1 WO2005066333A1 PCT/US2004/044028 US2004044028W WO2005066333A1 WO 2005066333 A1 WO2005066333 A1 WO 2005066333A1 US 2004044028 W US2004044028 W US 2004044028W WO 2005066333 A1 WO2005066333 A1 WO 2005066333A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- stabilizer
- composition
- virus
- viruses
- buffer
- Prior art date
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- 235000018977 lysine Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229940095293 mumps vaccine Drugs 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229960004854 viral vaccine Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24041—Use of virus, viral particle or viral elements as a vector
- C12N2710/24043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Definitions
- This invention relates to preparations of viruses, e.g. for vaccine or other pharmaceutical or research use, to their stabilization, and to processes of producing such preparations, as well as to their use, e.g. as vaccines or as virus vectors.
- compositions and methods useful in freezing, lyophilizing, or otherwise storing viable virus preparations for laboratory or vaccine use in order to preserve their activity are also known. These compositions typically contain multiple components including amino acids, peptides, proteins, carbohydrates, and buffers. Certain of these compositions are briefly described below.
- U.S. Pat. No. 6,258,362 provides a virus for use a vaccine in a pharmaceutical composition including polysaccharide, e.g. dextran, and/or a source of mixed aminoacids of vegetable or bacterial origin, a buffer, and a mono- or oligo-saccharide or derivative thereof.
- polysaccharide e.g. dextran
- 6,225,289 and 6,514,943 describe a virus-preserving composition consisting of a liquid carrier with a polysorbate 80, L-arginine, polyvinylpyrrolidone, or trehalose stabilizing agent that can be maintained at a temperature above 0° C. for a significant period of time while maintaining a satisfactory degree of viral activity.
- U.S. Pat. No. 5,616,487 relates to a stabilized retrovirus composition comprising a retrovirus and an alpha-hydro-omega. -hydroxypoly(oxyethylene) poly(oxypropylene)poly(oxyefhylene) block copolymer.
- EP 0028563 describe a stabilizer for liquid vaccines containing partially hydrolyzed gelatin, a monosaccharide or disaccharide, a cell culture medium, L-glutamic acid, L-arginine and buffer to maintain pH at from about 6.0 to about 6.5.
- EP 0295043 describes a stabilizer for measles, mumps or rubella virus including as a stabilizing agent lactose, saccharose, D-sorbitol, sodium glutamate and gelatin hydrolysate.
- EP 0252059 describes stabilizers containing lactose, sorbitol, dextran, casein hydrolysate, L-glutamate, EDTA and buffer at a pH 6.7-7.2.
- WO 96/29096 describes production of recombinant virus vectors with at least one additive selected among arginine, glutamic acid (or sodium salt thereof), serine, glucose, inositol, lactose, mannitol, sorbitol, trehalose and xylose.
- U.S. Pat. No. 4,985,244 describes stabilized measles, mumps or rubella virus vaccine stabilized with lactose, saccharose, D-sorbitol, sodiumj>lutamate and relatin hydrolyzate.
- U.S. Pat. No. 4,622,222 describes lyophilized duck virus hepatitis vaccine lyophilized in the presence of collidone, gelatin, glucose and sucrose.
- No. 4,500,512 describes live yellow fever virus vaccines with stabilizers comprising phosphate buffer, calcium and magnesium ions, lactose, sorbitol and amino acid selected from histidine, alanine, valine, threonine, arginine, methionine, hydroxyproline, lysine, isoleucine, phenylalanine, serine, preferably histidine and alanine.
- U.S. Pat. No. 5,792,643 demonstrates the stabilization of recombinant viruses using a saccharide, high molecular weight structural additive, a buffer and water.
- WO 93/18790 describes the lyophilization of viral vaccines in the presence of a modified starch as a protectant.
- JP06234659 and U.S. Pat. No. 6,039,958 disclose stabilized live varicella virus vaccines containing a stabilizer free from calcium and magnesium ions and including gelatin, a gelatin hydrolysate, or a chelating agent such as EDTA.
- JP06234659-A describes a herpesvirus vaccine suspended in a solution containing NaCl, KC1, Na2HPO4, KH2PO4, sucrose, L-glutamate, gelatin, gelatin hydrolysate and EDA-3Na.
- WO 98/28000 describes measles, mumps, rubella, VZV or HSV vaccine formulations including a 6-carbon polyhydric alcohol, a disaccharide and a buffer.
- No. 3,915,794 describes stable virus preparations in a buffered aqueous solution of pH 6.5-7.5 and containing polyvinylpyrrolidone, sugar, glutamate and chelating agent.
- U.S. Pat. No. 4,147,772 describes a lyophilised live virus vaccine in a composition containing partially hydrolysed gelatin, a 6-carbon polyhydric alcohol, cell culture medium and acidic buffer. It remains desirable to provide further forms of stabilized virus preparations, e.g. for vaccine use.
- the present invention provides a method and stabilizing composition ("stabilizer") for preserving viruses, such as viral vectors.
- the present invention provides a method for preserving a virus comprising preparing a stabilized liquid composition comprising a virus, a liquid carrier, and at least one stabilizing agent.
- the invention provides a stabilizing composition useful for long- term storage of viral vectors at temperatures below about 10°C.
- a further stabilizing composition is provided for adjusting titer and/or product volume prior to freeze-drying and packaging of the virus.
- the present invention provides compositions for stably storing and preserving the activity of viruses, including recombinant viruses, for use as expression vectors and/or vaccines.
- the compositions are useful in methods of preparing and storing such viruses without a significant decrease in viral activity. A significant decrease in viral activity is considered a drop in activity of more than about 10-20%.
- the term "activity” is used herein with reference to viability of the virus.
- the present invention can be utilized to preserve (e.g., store) "active" and/or "inactive” viruses.
- the terms "activity”, “active” and “inactive” refers to any suitable measure of the viability of a composition of a virus.
- the virus preparation is at least temporarily maintained in a composition that is in liquid form. In certain cases, it may be desirable to freeze-dry or otherwise process the virus preparation. With respect to the liquid, it is preferred that the liquid composition is a pharmaceutical composition.
- the pharmaceutically acceptable carrier can be a liquid carrier that contains a buffer (i.e., Tris) and a salt. Examples of suitable buffers ⁇ and salts, as well as other types of pharmaceutically acceptable carriers, are well known in the art.
- the temperature at which the liquid composition is maintained can be any suitable temperature to maintain the virus in its desired state over the time period of storage.
- the liquid composition is maintained at a temperature below 10 degrees C, (i.e., 5°C, -35°C). It is preferred that the stabilizing composition aid in maintaining the virus in the desired state (i.e., active, inactive) for various periods of time up to an including several weeks and/or months.
- the liquid composition can possess any suitable pH.
- a suitable pH in the context of the present invention is any pH where the virus is maintained in the liquid composition in a state capable of being later used for its intended purpose (i.e., active, inactive).
- the pH of the liquid composition desirably is about 6-9, 6-8.5, 6.5-8.5, 7- 8.5, 7.5-8.5, 6-8, 6.5-8, 7-8, 7.5-8, or 7- 7.5.
- the liquid composition has a pH somewhat above 7 but below about 8.0.
- the liquid composition can be placed (e.g., maintained or stored) in any suitable container.
- the container will comprise, consist essentially of, or consist of glass or plastic. Many different viruses may be utilized in practicing the present invention.
- Suitable viruses include, for example, Adeno viruses, Arbo viruses, Astro viruses, Bacteriophages, Enteroviruses, Gastroenteritis Viruses, Hantavirus, Coxsackie viruses, Hepatitis A Viruses, Hepatitis B Viruses, Hepatitis C Viruses, Herpesviruses (for example, Epstein Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV)), Influenza Viruses, Norwalk Viruses, Polio Viruses, Chordopoxviridae (i.e., Orthopoxvirus, vaccinia, MNA, ⁇ YVAC, Avipoxvirus, canarypox, ALNAC, ALNAC(2), fowlpox), Rhabdoviruses, Reoviruses Rhinoviruses, Rotavirus, Retroviruses, Baculoviridae, Caliciviridae
- Preferred viruses for use in practicing the present invention are poxviruses, in particular ALNAC.
- Other suitable viruses are known in the art as described in, for example, Fields et al., Virology (34th ed., Lippincott Williams & Wilkins (2001)).
- the stabilizer of the present invention include several components which together provide a stabilizing effect to a virus. With respect to recombinant viruses based on ALVAC, these have typically been stored as freeze- dried pellets containing sucrose, hydrolysates of casein and/or collagen, and phosphate-buffered physiological saline. These pellets are then re-hydrated in a pharmaceutically acceptable solution such as 0.4-0.9% ⁇ aCl.
- the new stabilizers which are useful for storing viral vectors such as ALVAC recombinants, among others, includes in various combinations and amounts, a sugar having cryopreservation abilities (i.e., sucrose, sorbitol), a salt (i.e., sodium glutamate), a buffer (i.e., Tris), a dispersing agent to maintain product appearance and functionality (i.e., polyvinyl pyrrolidone), essential and non-essential amino acids to preserve viablity, and urea to provide increased thermal stability to the final product.
- the liquid composition may include other substances, for example other stabilizing agents, buffers, or carriers.
- the pH of the stabilizer is about 7.25.
- composition A comprising a sugar having cryopreservation abilities (i.e., sucrose, sorbitol), a salt (i.e., sodium glutamate), a buffer (i.e., Tris), a dispersing agent to maintain product appearance and functionality (i.e., polyvinyl pyrrolidone), essential and non-essential amino acids to preserve viablity, and urea to provide increased thermal stability to the final product provides the ability to stably store viral vectors at temperatures below 10°C for long periods of time (i.e., three months).
- composition B is provided and contains approximately the same components as composition A but at about one-half the concentration as composition A.
- Composition B is useful for adjusting titers and/or volume prior to filling and/or freeze-drying.
- the new stabilizer provided herein allows for low-volume, high titer compositions of recombinant viral vectors. This allows for more efficient handling including but not limited to faster lyophilization processes.
- the present invention is further described in the following examples. The examples serve only to illustrate the invention and are not intended to limit the scope of the invention in any way.
- a novel stabilizer was developed and optimized in order to accommodate accommodate a reduction in the freeze-drying cycle of ALNAC-based expression vectors from 72 hours to 24 hours. As such, a product with the same titer parameters could be produced in a fill volume one third that of the original formulation (the fill volume being reduced from l.OmL to 0.3mL).
- the stabilizer is prepared as shown in Table I as follows.
- the amino acid mixes (essential and non-essential) are made up as solutions in WFI to the required concentrations.
- the remaining ingredients (which are all powders) are weighed out and added to the mixing vessel.
- the amino acid solutions are added with stirring.
- the pH is adjusted as required (approximately 7.2) and then made up to volume with WFI.
- the stabilizer is sterile filtered before use.
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- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
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- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
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- Microbiology (AREA)
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- General Health & Medical Sciences (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US53331703P | 2003-12-30 | 2003-12-30 | |
US60/533,317 | 2003-12-30 |
Publications (1)
Publication Number | Publication Date |
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WO2005066333A1 true WO2005066333A1 (en) | 2005-07-21 |
Family
ID=34748884
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2004/044028 WO2005066333A1 (en) | 2003-12-30 | 2004-12-30 | Stabilizing compositions for recombinant viruses |
Country Status (1)
Country | Link |
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WO (1) | WO2005066333A1 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007035455A2 (en) * | 2005-09-16 | 2007-03-29 | Merial Limited | Stabilizers for freeze-dried vaccines |
WO2007056847A1 (en) | 2005-11-21 | 2007-05-24 | Sanofi Pasteur Limited | Stabilizing formulations for recombinant viruses |
WO2014053571A1 (en) | 2012-10-02 | 2014-04-10 | Transgene Sa | Virus-containing formulation and use thereof |
US9044498B2 (en) | 2010-12-02 | 2015-06-02 | Oncolytics Biotech Inc. | Lyophilized viral formulations |
US9045728B2 (en) | 2010-12-02 | 2015-06-02 | Oncolytics Biotech Inc. | Liquid viral formulations |
WO2016087457A1 (en) * | 2014-12-01 | 2016-06-09 | Transgene Sa | Stable liquid vaccinia virus formulations |
EP2851087B1 (en) | 2006-11-07 | 2017-04-19 | Sanofi Pasteur Biologics, LLC | Stabilization of vaccines by lyophilization |
WO2018027075A1 (en) * | 2016-08-03 | 2018-02-08 | Takeda Vaccines, Inc. | Compositions and methods for stabilizing flaviviruses with improved formulations |
WO2018050872A1 (en) * | 2016-09-16 | 2018-03-22 | Leukocare Ag | A novel method for obtaining efficient viral vector-based compositions for vaccination or gene therapy |
WO2020049151A1 (en) | 2018-09-06 | 2020-03-12 | Bavarian Nordic A/S | Storage improved poxvirus compositions |
WO2021028559A1 (en) * | 2019-08-14 | 2021-02-18 | Leukocare Ag | Method for obtaining efficient compositions comprising viral vectors for vaccination or gene therapy |
WO2021180943A1 (en) | 2020-03-12 | 2021-09-16 | Bavarian Nordic A/S | Compositions improving poxvirus stability |
US11510871B2 (en) | 2016-09-16 | 2022-11-29 | Leukocare Ag | Method for producing low viscous and highly concentrated biopharmaceutical drug products in liquid formulation |
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Cited By (35)
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WO2007035455A3 (en) * | 2005-09-16 | 2007-07-26 | Merial Ltd | Stabilizers for freeze-dried vaccines |
CN101312742B (en) * | 2005-09-16 | 2012-07-25 | 梅瑞尔有限公司 | Stabilizers for freeze-dried vaccines |
WO2007035455A2 (en) * | 2005-09-16 | 2007-03-29 | Merial Limited | Stabilizers for freeze-dried vaccines |
WO2007056847A1 (en) | 2005-11-21 | 2007-05-24 | Sanofi Pasteur Limited | Stabilizing formulations for recombinant viruses |
AU2006315026B2 (en) * | 2005-11-21 | 2012-11-22 | Sanofi Pasteur Limited | Stabilizing formulations for recombinant viruses |
KR101357685B1 (en) | 2005-11-21 | 2014-02-06 | 사노피 파스퇴르 리미티드 / 사노피 파스퇴르 리미떼 | Stabilizing formulations for recombinant viruses |
EP2851087B1 (en) | 2006-11-07 | 2017-04-19 | Sanofi Pasteur Biologics, LLC | Stabilization of vaccines by lyophilization |
US9045728B2 (en) | 2010-12-02 | 2015-06-02 | Oncolytics Biotech Inc. | Liquid viral formulations |
US9610352B2 (en) | 2010-12-02 | 2017-04-04 | Oncolytics Biotech Inc. | Lyophilized viral formulations |
US9610309B2 (en) | 2010-12-02 | 2017-04-04 | Oncolytics Biotech Inc. | Liquid viral formulations |
US9044498B2 (en) | 2010-12-02 | 2015-06-02 | Oncolytics Biotech Inc. | Lyophilized viral formulations |
US10111947B2 (en) | 2012-10-02 | 2018-10-30 | Transgene S.A. | Virus-containing formulation and use thereof |
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CN107206063B (en) * | 2014-12-01 | 2021-09-28 | 特兰斯吉恩股份有限公司 | Stable liquid vaccinia virus formulations |
CN107206063A (en) * | 2014-12-01 | 2017-09-26 | 特兰斯吉恩股份有限公司 | Stable liquid vaccinia virus preparation |
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US10517943B2 (en) | 2014-12-01 | 2019-12-31 | Transgene S.A. | Stable liquid vaccinia virus formulations |
KR20170091653A (en) * | 2014-12-01 | 2017-08-09 | 트랜스진 에스.에이. | Stable liquid vaccinia virus formulations |
US10835597B2 (en) | 2016-08-03 | 2020-11-17 | Takeda Vaccines, Inc. | Compositions and methods for stabilizing flaviviruses with improved formulations |
CN109789200A (en) * | 2016-08-03 | 2019-05-21 | 武田疫苗股份有限公司 | Make the stabilized composition of flavivirus and method with improved preparaton |
WO2018027075A1 (en) * | 2016-08-03 | 2018-02-08 | Takeda Vaccines, Inc. | Compositions and methods for stabilizing flaviviruses with improved formulations |
AU2017305498B2 (en) * | 2016-08-03 | 2023-03-30 | Takeda Vaccines, Inc. | Compositions and methods for stabilizing flaviviruses with improved formulations |
US11701421B2 (en) | 2016-08-03 | 2023-07-18 | Takeda Vaccines, Inc. | Compositions and methods for stabilizing flaviviruses with improved formulations |
WO2018050872A1 (en) * | 2016-09-16 | 2018-03-22 | Leukocare Ag | A novel method for obtaining efficient viral vector-based compositions for vaccination or gene therapy |
US11166915B2 (en) | 2016-09-16 | 2021-11-09 | Leukocare Ag | Method for obtaining efficient viral vector-based compositions for vaccination or gene therapy |
US11510871B2 (en) | 2016-09-16 | 2022-11-29 | Leukocare Ag | Method for producing low viscous and highly concentrated biopharmaceutical drug products in liquid formulation |
WO2020049151A1 (en) | 2018-09-06 | 2020-03-12 | Bavarian Nordic A/S | Storage improved poxvirus compositions |
WO2021028559A1 (en) * | 2019-08-14 | 2021-02-18 | Leukocare Ag | Method for obtaining efficient compositions comprising viral vectors for vaccination or gene therapy |
WO2021180943A1 (en) | 2020-03-12 | 2021-09-16 | Bavarian Nordic A/S | Compositions improving poxvirus stability |
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