.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,040,136

« Back to Dashboard

Details for Patent: 6,040,136

Title: Enrichment method for variant proteins with altered binding properties
Abstract:A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered binding properties for their respective receptor molecules is provided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated to form a library of structurally related fusion proteins that are expressed in low quantity on the surface of a phagemid particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates. Disclosed are preferred phagemid expression vectors and selected human growth hormone variants.
Inventor(s): Garrard; Lisa J. (Burlingame, CA), Henner; Dennis J. (Pacifica, CA), Bass; Steven (Redwood City, CA), Greene; Ronald (Durham, NC), Lowman; Henry B. (Hercules, CA), Wells; James A. (Burlingame, CA), Matthews; David J. (San Francisco, CA)
Assignee: Genentech, Inc. (South San Francisco, CA)
Filing Date:Sep 03, 1997
Application Number:08/923,854
Claims:1. A phagemid expression vector, comprising a transcription regulatory element operably linked to a gene fusion encoding a fusion protein, wherein the gene fusion comprises a first gene encoding a polypeptide and a second gene encoding at least a portion of a phage coat protein, the vector not containing a further gene encoding a mature phage coat protein.

2. The vector of claim 1, prepared by cloning the fusion gene into a bacterial expression plasmid containing a phage origin of replication.

3. The vector of claim 1, comprising a bacterial promoter.

4. The vector of claim 3, wherein the promoter is a lac promoter of a pho promoter.

5. The vector of claim 1, comprising a bacteriophage promoter.

6. The vector of claim 1, wherein the coat protein is encoded by gene III of a filamentous phage.

7. The vector of claim 6, wherein the polypeptide is fused to a carboxy terminal domain of a polypeptide encoded by gene III.

8. The vector of claim 7, wherein the polypeptide is fused to residue 198 of the polypeptide encoded by gene III.

9. The vector of claim 7, wherein the polypeptide is an antibody or a fragment thereof.

10. The vector of claim 7, wherein the polypeptide is a serine protease.

11. The vector of claim 7, wherein the polypeptide is protein A or a fragment thereof.

12. The vector of claim 7, wherein the fusion gene contains a suppressible stop codon between the first gene and the second gene.

13. A phagemid particle, comprising the vector of claim 1.

14. The vector of claim 1, wherein the polypeptide is selected from the group consisting of human growth hormone, bovine growth hormone, insulin A-chain, insulin B-chain, proinsulin, human tissue-type plasminogen activator, thrombin, tumor necrosis factor .alpha., tumor necrosis factor .beta., tissue factor protein, vascular endothelial growth factor, thrombopoietin, protein A, integrins, nerve growth factors, platelet growth factors, transforming growth factors, insulin-like growth factors, DNase, erythropoietin, interferons, interleukins, atrial natriuretic peptides, immunoglobulins and fragments thereof.

15. The vector of claim 14, wherein the polypeptide is protein A or a fragment thereof.

16. A phagemid expression vector, comprising a transcription regulatory element operably linked to a gene fusion encoding a fusion protein, wherein the gene fusion comprises a first gene encoding a polypeptide and a second gene encoding at least a portion of a phage cost protein; the vector not containing a complete phage genome.

17. The vector of claim 16, prepared by cloning the fusion gene into a bacterial expression plasmid containing a phage origin of replication.

18. The vector of claim 16, comprising a bacterial promoter.

19. The vector of claim 18, wherein the promoter is a lac promoter or a pho promoter.

20. The vector of claim 16, comprising a bacteriophage promoter.

21. The vector of claim 16, wherein the coat protein is encoded by gene III of a filamentous phage.

22. The vector of claim 21, wherein the polypeptide is fused to a carboxy terminal domain of a polypeptide encoded by gene III.

23. The vector of claim 22, wherein the polypeptide is fused to residue 198 of the polypeptide encoded by gene III.

24. The vector of claim 22, wherein the polypeptide is an antibody or a fragment thereof.

25. The vector of claim 22, wherein the polypeptide is a serine protease.

26. The vector of claim 22, wherein the polypeptide is protein A or a fragment thereof.

27. The vector of claim 22, wherein the fusion gene contains a suppressible stop codon between the first gene and the second gene.

28. A phagemid particle, comprising the vector of claim 16.

29. The vector of claim 16, wherein the polypeptide is selected from the group consisting of human growth hormone, bovine growth hormone, insulin A-chain, insulin B-chain, proinsulin, human tissue-type plasminogen activator, thrombin, tumor necrosis factor .alpha., tumor necrosis factor .beta., tissue factor protein, vascular endothelial growth factor, thrombopoietin, protein A, integrins, nerve growth factors, platelet growth factors, transforming growth factors, insulin-like growth factors, DNase, erythropoietin, interferons, interleukins, atrial natriuretic peptides, immunoglobulins and fragments thereof.

30. The vector of claim 29, wherein the polypeptide is protein A or a fragment thereof.

31. A phagemid expression vector, comprising a transcription regulatory element operably linked to a gene fusion encoding a fusion protein, wherein the gene fusion comprises a first gene encoding a polypeptide and a second gene encoding at least a portion of a phage coat protein, wherein transformation of suitable host cells with the vector requires co-infection with a helper phage to produce infective phagemid particles.

32. The vector of claim 31, prepared by cloning the fusion gene into a bacterial expression plasmid containing a phage origin of replication.

33. The vector of claim 31, comprising a bacterial promoter.

34. The vector of claim 33, wherein the promoter is a lac promoter or a pho promoter.

35. The vector of claim 31, comprising a bacteriophage promoter.

36. The vector of claim 31, wherein the coat protein is encoded by gene III of a filamentous phage.

37. The vector of claim 36, wherein the polypeptide is fused to a carboxy terminal domain of a polypeptide encoded by gene III.

38. The vector of claim 37, wherein the polypeptide is fused to residue 198 of the polypeptide encoded by gene III.

39. The vector of claim 37, wherein the polypeptide is an antibody or a fragment thereof.

40. The vector of claim 37, wherein the polypeptide is a serine protease.

41. The vector of claim 37, wherein the polypeptide is protein A or a fragment thereof.

42. The vector of claim 37, wherein the fusion gene contains a suppressible stop codon between the first gene and the second gene.

43. A phagemid particle, comprising the vector of claim 31.

44. The vector of claim 31, wherein the polypeptide is selected from the group consisting of human growth hormone, bovine growth hormone, insulin A-chain, insulin B-chain, proinsulin, human tissue-type plasminogen activator, thrombin, tumor necrosis factor .alpha., tumor necrosis factor .beta., tissue factor protein, vascular endothelial growth factor, thrombopoietin, protein A, integrins, nerve growth factors, platelet growth factors, transforming growth factors, insulin-like growth factors, DNase, erythropoietin, interferons, interleukins, atrial natriuretic peptides, immunoglobulins and fragments thereof.

45. The vector of claim 44, wherein the polypeptide is protein A or a fragment thereof.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc