SI8912489B - Novi IL-2 receptor specifični humani imunoglobulini - Google Patents
Novi IL-2 receptor specifični humani imunoglobulini Download PDFInfo
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- SI8912489B SI8912489B SI8912489A SI8912489A SI8912489B SI 8912489 B SI8912489 B SI 8912489B SI 8912489 A SI8912489 A SI 8912489A SI 8912489 A SI8912489 A SI 8912489A SI 8912489 B SI8912489 B SI 8912489B
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- 108060003951 Immunoglobulin Proteins 0.000 title claims 29
- 102000018358 immunoglobulin Human genes 0.000 title claims 29
- 102000010789 Interleukin-2 Receptors Human genes 0.000 title claims 4
- 229940072221 immunoglobulins Drugs 0.000 title claims 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 6
- 150000001413 amino acids Chemical class 0.000 claims 9
- 102000004169 proteins and genes Human genes 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 102000040430 polynucleotide Human genes 0.000 claims 5
- 108091033319 polynucleotide Proteins 0.000 claims 5
- 239000002157 polynucleotide Substances 0.000 claims 5
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 claims 4
- 238000006467 substitution reaction Methods 0.000 claims 4
- 230000000295 complement effect Effects 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 1
- 108010002350 Interleukin-2 Proteins 0.000 claims 1
- 102000000588 Interleukin-2 Human genes 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 102000055277 human IL2 Human genes 0.000 claims 1
- 230000001900 immune effect Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 abstract 1
- 108091035707 Consensus sequence Proteins 0.000 abstract 1
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
- C07K16/085—Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
- C07K16/087—Herpes simplex virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
- C07K16/085—Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
- C07K16/088—Varicella-zoster virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/249—Interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
- C07K16/465—Igs containing CDR-residues from one specie grafted between FR-residues from another with additional modified FR-residues
-
- 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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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- 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
-
- 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
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- Proteomics, Peptides & Aminoacids (AREA)
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Claims (18)
1 PROTEIN DESIGN LABS, Inc. EP 451216 Mountain View US-1/333 94043 CALIFORNIA USA PATENTNI ZAHTEVKI 1. Uporaba vsaj ene substitucije amino kisline izven komplementarno določujočih področij (CDR-ji), kot je definirano v Kabat et.al. ("Sequences of Proteins of immunological interest", Kabat E. et. al. US Department of Health and Human Services, (1983)) skupaj s Chothia et. al., (Chothia and Lesk, J. Mol. Biol., 196:· 901-917 (1987)) pri izdelavi humaniziranega imunoglobulina, značilna po tem, da je omenjena substitucija amino kisline iz ne-CDR variabilnega področja nehumanega donorja imunoglobulina in kjer zaporedje aminokislin variabilnega področja humaniziranega imunoglobulina, ki je drugačno od tistih, ki vsebujejo CDR-je, obsega vsaj 70 amino kislinskih ostankov, ki so identični zaporedju amino kislin variabilnega področja akceptorja humanega imunoglobulina in kjer so CDR-ji iz variabilnega področja omenjenega imunoglobulina nehumanega donorja.
2. Uporaba po zahtevku 1, značilna po tem, da je omenjeni humanizirani imunoglobulin specifično reaktiven s p55 Tac proteinom in je zmožen inhibirati vezavo humanega interleukina-2 (IL-2) na humani IL-2 receptor, ali pa je zmožen vezati se na humani IL-2 receptor.
3. Uporaba po zahtevku 2, značilna po tem, da omenjeni humanizirani imunoglobulin kaže afiniteto vezave s humanim IL-2 receptorjem približno 108 M-1 ali višjo. z
4.Uporaba po zahtevku 2 ali po zahtevku 3, značilna po tem, da so zrela proteinska zaporedja lahkih in težkih variabilnih področij omenjenega humaniziranega imunoglobulina skladna z zrelimi proteinskimi zaporedji v SEQ ID NO:l in SEQ ID NO:2.
5. Uporaba po kateremkoli zahtevku od 1 do 4, značilna po tem, da je omenjeni humanizirani imunoglobulin izotip imunoglobulina IgGi.
6. Uporaba po kateremkoli zahtevku od 1 do 5, značilna po tem, da je omenjena substitucija sosednja s CDR.
7. Metoda gradnje humanizirane imunoglobulinske verige, ki ima mrežno (ogrodno) področje iz humanega akceptorskega imunoglobulina in komplementarno določujoče področje (CDR) iz donorskega imunoglobulina, sposobnega vezave na antigen, značilen po tem, da obsega stopnje substitucije vsaj ene mrežne (ogrodne) ne-CDR amino kisline akceptornega imunoglobulina z ustrezno amino kislino iz donorskega imunoglobulina na položaju v imunoglobulinu kjer: a) je amino kislina v humanem mrežnem (ogrodnem) področju akceptorskega imunoglobulina redka za omenjeni položaj, ustrezna amino kislina v donorskem imunoglobulinu pa je obča za omenjeni položaj v humanih imunoglobulinskih sekvencah; ali 4 b) amino kislina je tik ob enem izmed CDR; ali pa c) je za amino kislino predvideno, da ima atom stranske verige, ki je sposoben sodelovati z antigenom ali s CDR humaniziranega imunoglobulina. 3 c r r r
8. Metoda po zahtevku 7, značilna po tem, da so vsaj tri aminokisline omenjenega ne-CDR mrežnega (ogrodnega) področja substituirane z amino kislinami iz imunoglobulina donorja, izbranimi po kriterijih (a),(b) ali (c).
9. Metoda po zahtevku 8, značilna po tem, da je vsaj ena izmed amino kislin substituiranih iz donorja, sosednja CDR.
10.Metoda po zahtevkih 7 do 9, značilna po tem, da so zrela proteinska zaporedja lahkih in težkih variabilnih področij omenjenega humaniziranega imunoglobulina skladna z zrelimi proteinskimi zaporedji v SEQ ID NO: 1 in SEQ ID NO:2.
11. Humanizirana imunoglobulinska veriga značilna po tem, da jo lahko pridobimo z uporabo po kateremkoli zahtevku od 1 do 6.
12. Humanizirana imunoglobulinska veriga značilna po tem, da jo lahko pridobimo z metodo po kateremkoli zahtevku od 7 do 10.
13. Humanizirani imunoglobulin značilen po tem, da obsega težke in lahke verige po zahtevku 11 ali po zahtevku 12.
14. Polinukleotid, značilen po tem, da obsega prvo zaporedje, ki kodira humano-podobne imunoglobuline ne-CDR mrežnega (ogrodnega) področja in drugo zaporedje, ki kodira eno ali več CDR, kjer omenjeni polinukleotid po ekpresiji kodira imunoglobulinsko verigo po zahtveku 11 ali po zahtevku 12. « · C Γ m n r «* ···♦ err 9 r 9 e * < * · Γ r r r- 9. 9 r- r r r r r c e r ,· f r r f» * r r, Λι f 4
15. Polinukleotidi po zahtevku 14, značilni po tem, da po ekspresiji kodirajo verige, ki določajo imunoglobulin po zahtevku 13.
16. Celična linija, značilna po tem, da je transfektirana s polinukleotidom ali polinukleotidi po zahtevku 14 ali po zahtevku 15.
17. Farmacevtski preparat, značilen po tem, da obsega humanizirani imunoglobulin po zahtevku 13, formuliran v farmacevtsko sprejemljivi obliki.
18. Metoda izdelave humaniziranega imunoglobulina (Ig), ki ima komplementarno določujoča področja (CDR) iz Ig donorja, združenega z mrežnim (ogrodnim) področjem iz humanih Ig akceptorskih lahkih in težkih verig, značilna po tem, da obsega: a. primerjavo mrežnih (ogrodnih) področij ali variabilnih področij amino kislinskih zaporedij lahkih in težkih verig Ig donorja, z odgovarjajočimi zaporedji v zbirki humanih Ig verig; b. izbira zaporedij iz zbirke, ki so vsaj 65% enaka z odgovarjajočim zaporedjem mrežnega (ogrodnega) področja donorja, za zagotovitev mrežnih (ogrodnih) področij lahkih in težkih verig humanega Ig akceptorja; c. združevanje CDR-jev iz Ig donorja in mrežnih (ogrodnih) področij iz izbranih zaporedij akceptorjev. za PROTEIN DESIGN LABS INC
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29097588A | 1988-12-28 | 1988-12-28 | |
| US31025289A | 1989-02-13 | 1989-02-13 | |
| YU248989A YU48700B (sh) | 1988-12-28 | 1989-12-28 | Postupak za proizvodnju humaniziranog imunoglobulinskog lanca |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI8912489A SI8912489A (sl) | 1999-02-28 |
| SI8912489B true SI8912489B (sl) | 2000-04-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI8912489A SI8912489B (sl) | 1988-12-28 | 1989-12-28 | Novi IL-2 receptor specifični humani imunoglobulini |
Country Status (31)
| Country | Link |
|---|---|
| EP (6) | EP1491556B1 (sl) |
| JP (6) | JP2828340B2 (sl) |
| KR (1) | KR0178385B1 (sl) |
| CN (1) | CN1057013C (sl) |
| AT (2) | ATE133452T1 (sl) |
| AU (1) | AU647383B2 (sl) |
| BG (1) | BG61095B2 (sl) |
| CA (2) | CA2006865C (sl) |
| CZ (1) | CZ418691A3 (sl) |
| DD (1) | DD296964A5 (sl) |
| DE (14) | DE122009000071I1 (sl) |
| DK (2) | DK119191A (sl) |
| ES (5) | ES2440825T3 (sl) |
| FI (1) | FI108797B (sl) |
| FR (1) | FR14C0070I1 (sl) |
| HR (1) | HRP920500B1 (sl) |
| HU (1) | HU211174A9 (sl) |
| IE (1) | IE20000331A1 (sl) |
| IL (2) | IL162181A (sl) |
| LU (8) | LU90411I2 (sl) |
| MC (1) | MC2146A1 (sl) |
| NL (8) | NL990020I2 (sl) |
| NO (9) | NO310473B1 (sl) |
| NZ (2) | NZ231984A (sl) |
| PT (1) | PT92758B (sl) |
| RU (1) | RU2126046C1 (sl) |
| SG (1) | SG78258A1 (sl) |
| SI (1) | SI8912489B (sl) |
| WO (1) | WO1990007861A1 (sl) |
| YU (1) | YU48700B (sl) |
| ZA (1) | ZA899956B (sl) |
Families Citing this family (1057)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5800815A (en) * | 1903-05-05 | 1998-09-01 | Cytel Corporation | Antibodies to P-selectin and their uses |
| US5851526A (en) * | 1985-04-19 | 1998-12-22 | Ludwig Institute For Cancer Research | Methods of treating colon cancer utilizing tumor-specific antibodies |
| US5449760A (en) * | 1987-12-31 | 1995-09-12 | Tanox Biosystems, Inc. | Monoclonal antibodies that bind to soluble IGE but do not bind IGE on IGE expressing B lymphocytes or basophils |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US7247453B1 (en) * | 1988-12-30 | 2007-07-24 | Oklahoma Medical Research Foundation | Calcium binding recombinant antibody against protein C |
| DE3900534A1 (de) * | 1989-01-10 | 1990-07-12 | Boehringer Mannheim Gmbh | Diagnostischer nachweis unter verwendung von chimaeren antikoerpern |
| AU640400B2 (en) | 1989-08-07 | 1993-08-26 | Peptide Technology Ltd. | Tumour necrosis factor binding ligands |
| US20030225254A1 (en) | 1989-08-07 | 2003-12-04 | Rathjen Deborah Ann | Tumour necrosis factor binding ligands |
| US6750325B1 (en) | 1989-12-21 | 2004-06-15 | Celltech R&D Limited | CD3 specific recombinant antibody |
| US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| GR1001050B (el) * | 1990-01-09 | 1993-04-28 | Protein Design Labs Inc | Νεος il-2 υποδοχευς ιδιαζοντων ανθρωπινων ανοσοσφαιρινων. |
| HUT60768A (en) | 1990-03-16 | 1992-10-28 | Sandoz Ag | Process for producing cd25 fixing molecules |
| GB9020282D0 (en) | 1990-09-17 | 1990-10-31 | Gorman Scott D | Altered antibodies and their preparation |
| US5858725A (en) * | 1990-10-10 | 1999-01-12 | Glaxo Wellcome Inc. | Preparation of chimaeric antibodies using the recombinant PCR strategy |
| US5994510A (en) * | 1990-12-21 | 1999-11-30 | Celltech Therapeutics Limited | Recombinant antibodies specific for TNFα |
| DE69233153T2 (de) * | 1991-03-06 | 2004-05-27 | Merck Patent Gmbh | Humanisierte monoklonale antikörper |
| IL101147A (en) * | 1991-03-07 | 2004-06-20 | Gen Hospital Corp | Redirection of cellular immunity by receptor chimeras |
| WO1992017505A1 (en) * | 1991-04-05 | 1992-10-15 | Board Of Regents Of The University Of Washington | Monoclonal antibodies to stem cell factor receptors |
| JP3370324B2 (ja) * | 1991-04-25 | 2003-01-27 | 中外製薬株式会社 | ヒトインターロイキン−６受容体に対する再構成ヒト抗体 |
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