NZ772550B2 - Multi-chain chimeric polypeptides and uses thereof - Google Patents
Multi-chain chimeric polypeptides and uses thereofInfo
- Publication number
- NZ772550B2 NZ772550B2 NZ772550A NZ77255019A NZ772550B2 NZ 772550 B2 NZ772550 B2 NZ 772550B2 NZ 772550 A NZ772550 A NZ 772550A NZ 77255019 A NZ77255019 A NZ 77255019A NZ 772550 B2 NZ772550 B2 NZ 772550B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- sequence
- domain
- chimeric polypeptide
- target
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5418—IL-7
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5434—IL-12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5443—IL-15
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/283—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/36—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
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- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains which comprise soluble IL-15; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains which comprise a sushi domain from an alpha chain of ILl5Ra and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.
Claims (28)
1. A multi-chain chimeric polypeptide comprising: (a) a first chimeric polypeptide comprising: (i) a first target-binding domain; (ii) a soluble tissue factor domain comprising a ce that is at least 90% identical to SEQ ID NO: 1; and (iii) a first domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO: 14; (b) a second chimeric ptide comprising: (i) a second domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO: 28; and (ii) a second target-binding , wherein the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains; and the first target-binding domain and the second target-binding domain each comprise a soluble TGF-ß receptor II (TGF-ßRII) and each comprise a sequence that is at least 90% identical to SEQ ID NO: 85.
2. The multi-chain chimeric polypeptide of claim 1, n the first target-binding domain and the e tissue factor domain directly abut each other in the first chimeric polypeptide.
3. The chain chimeric polypeptide of claim 1, wherein the first chimeric polypeptide further comprises a linker ce between the first target-binding domain and the soluble tissue factor domain in the first chimeric polypeptide.
4. The multi-chain chimeric polypeptide of any one of claims 1-3, wherein the soluble tissue factor domain and the first domain of the pair of affinity domains directly abut each other in the first chimeric polypeptide.
5. The multi-chain chimeric polypeptide of any one of claims 1-3, wherein the first chimeric polypeptide further comprises a linker sequence between the soluble tissue factor domain and the first domain of the pair of affinity domains in the first chimeric polypeptide.
6. The multi-chain chimeric polypeptide of any one of claims 1-5, n the second domain of the pair of ty domains and the second target-binding domain directly abut each other in the second ic polypeptide.
7. The multi-chain chimeric polypeptide of any one of claims 1-5, wherein second ic polypeptide further comprises a linker sequence between the second domain of the pair of affinity s and the second -binding domain in the second chimeric polypeptide.
8. A composition comprising any of the multi-chain chimeric ptides of claims
9. Use of any of the multi-chain chimeric polypeptides of claims 1-7 or the composition of claim 8 in the manufacture of a medicament for the treatment of a cancer cell, an infected cell, or a senescent cell in a human subject in need thereof.
10. Nucleic acid encoding any of the multi-chain chimeric polypeptides of any one of claims 1-7.
11. The multi-chain chimeric polypeptide of claim 1, wherein the first -binding domain comprises a sequence that is at least 95% identical to SEQ ID NO: 85.
12. The multi-chain chimeric polypeptide of claim 1, wherein the first target-binding domain comprises a sequence that is at least 99% identical to SEQ ID NO: 85.
13. The multi-chain chimeric polypeptide of claim 1, wherein the first target-binding domain comprises a sequence of SEQ ID NO: 85.
14. The multi-chain chimeric polypeptide of claim 1, wherein: the first chimeric ptide comprises a sequence of SEQ ID NO: 133; and the second chimeric polypeptide comprises a sequence of SEQ ID NO: 177.
15. The multi-chain chimeric polypeptide of claim 14, wherein: the first chimeric polypeptide ses a sequence of SEQ ID NO: 135; and the second chimeric ptide comprises a sequence of SEQ ID NO: 92.
16. The multi-chain chimeric polypeptide of claim 1, n the second targetbinding domain ses a sequence that is at least 95% identical to SEQ ID NO: 85.
17. The multi-chain ic polypeptide of claim 1, wherein the second targetbinding domain comprises a sequence that is at least 99% identical to SEQ ID NO: 85.
18. The multi-chain chimeric polypeptide of claim 1, wherein the second targetbinding domain comprises a sequence of SEQ ID NO: 85.
19. The chain chimeric polypeptide of claim 1, wherein the human soluble tissue factor domain does not initiate blood coagulation.
20. A composition comprising the multi-chain chimeric polypeptide of claim 1.
21. The multi-chain chimeric polypeptide of claim 1, wherein: the first and second target-binding domain each comprise a sequence that is at least 95% identical to SEQ ID NO: 85; the soluble tissue factor domain is at least 95% identical to SEQ ID NO: 1; the first domain of the pair of ty domains comprises a sequence that is at least 95% identical to SEQ ID NO: 14; and the second domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 28.
22. The multi-chain chimeric polypeptide of claim 1, wherein the first domain of the pair of ty domains comprises a sequence that is at least 95% identical to SEQ ID NO: 14, and the second domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 28.
23. The multi-chain chimeric ptide of claim 1, wherein: the first and second target-binding domain each se a sequence that is at least 99% identical to SEQ ID NO: 85; the soluble tissue factor domain is at least 99% identical to SEQ ID NO: 1; the first domain of the pair of affinity domains comprises a sequence that is at least 99% identical to SEQ ID NO: 14; and the second domain of the pair of affinity s comprises a sequence that is at least 99% identical to SEQ ID NO: 28.
24. The multi-chain chimeric polypeptide of claim 1, wherein the first domain of the pair of affinity domains comprises a sequence that is at least 99% identical to SEQ ID NO: 14, and the second domain of the pair of affinity domains comprises a sequence that is at least 99% identical to SEQ ID NO: 28.
25. The multi-chain chimeric polypeptide of claim 1, wherein the first chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 133, and the second chimeric polypeptide comprises a sequence that is at least 90% cal to SEQ ID NO: 177.
26. The multi-chain chimeric polypeptide of claim 1, wherein the first chimeric polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO: 133, and the second chimeric polypeptide comprises a ce that is at least 95% identical to SEQ ID NO: 177.
27. The multi-chain chimeric polypeptide of claim 1, wherein the first chimeric polypeptide comprises a sequence that is at least 99% identical to SEQ ID NO: 133, and the second chimeric polypeptide comprises a sequence that is at least 99% identical to SEQ ID NO: 177.
28. A multi-chain chimeric polypeptide sing: (a) a first chimeric polypeptide comprising: (i) a first target-binding ; (ii) a soluble tissue factor domain comprising a sequence that is at least 90% identical to SEQ ID NO: 1; and (iii) a first domain of a pair of affinity domains comprising a sequence that is at least 90% cal to SEQ ID NO: 14; and (b) a second chimeric polypeptide comprising: (i) a second target-binding domain; and (ii) a second domain of a pair of affinity s comprising a sequence that is at least 90% identical to SEQ ID NO: 28, wherein the first chimeric polypeptide and the second chimeric polypeptide associate through the g of the first domain and the second domain of the pair of affinity domains; and wherein: (A) the first target-binding domain comprises a sequence that is at least 90% cal to SEQ ID NO: 11 and the second target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 78, (B) the first target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 78 and the second target-binding domain comprises a sequence that is at least 90% cal to SEQ ID NO: 11; (C) the first target-binding domain comprises a sequence at least 90% identical to SEQ ID NO: 16 and the second target-binding domain comprises a first sequence that is at least 90% identical to SEQ ID NO: 66 and a second sequence that is at least 90% identical to SEQ ID NO: 68; or (D) the first target-binding domain comprises a first sequence that is at least 90% identical to SEQ ID NO: 66 and a second sequence that is at least 90% identical to SEQ ID NO: 68, and the second target-binding domain comprises a ce at least 90% identical to SEQ ID NO: 16. ?ga W..............................?t.............................. \\\\\\\\\\\\‘ ~ \\\\\\\\\\\\
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862725043P | 2018-08-30 | 2018-08-30 | |
| US201862725010P | 2018-08-30 | 2018-08-30 | |
| US201862724969P | 2018-08-30 | 2018-08-30 | |
| US201862746832P | 2018-10-17 | 2018-10-17 | |
| US201862749007P | 2018-10-22 | 2018-10-22 | |
| US201862749506P | 2018-10-23 | 2018-10-23 | |
| US201962816683P | 2019-03-11 | 2019-03-11 | |
| US201962817241P | 2019-03-12 | 2019-03-12 | |
| US201962817230P | 2019-03-12 | 2019-03-12 | |
| US201962881088P | 2019-07-31 | 2019-07-31 | |
| PCT/US2019/048881 WO2020047299A1 (en) | 2018-08-30 | 2019-08-29 | Multi-chain chimeric polypeptides and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ772550A NZ772550A (en) | 2025-08-29 |
| NZ772550B2 true NZ772550B2 (en) | 2025-12-02 |
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