IL132251A - NGF VARIANTS HAVING AMINO ACID SUBSTITUTIONS THAT IMPART trkC BINDING - Google Patents
NGF VARIANTS HAVING AMINO ACID SUBSTITUTIONS THAT IMPART trkC BINDINGInfo
- Publication number
- IL132251A IL132251A IL132251A IL13225199A IL132251A IL 132251 A IL132251 A IL 132251A IL 132251 A IL132251 A IL 132251A IL 13225199 A IL13225199 A IL 13225199A IL 132251 A IL132251 A IL 132251A
- Authority
- IL
- Israel
- Prior art keywords
- ngf variant
- ngf
- variant
- peripheral neuropathy
- neural disorder
- Prior art date
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (54)
1. A nerve growth factor (NGF) variant comprising NGF having a T29 substitution other than T29I, and having substitutions at amino acid positions G23 and H84, and either VI 8 or V20 that impart trkC binding, wherein the variant binds trkC.
2. The NGF variant of claim 1, wherein V20 is substituted.
3. The NGF variant of claim 1, further comprising a substitution of any one or more of F86 and T81.
4. The NGF variant of claim 1, wherein the substitutions are selected from the group consisting of G23T, G23S, G23A, H84Q, H84N, V18E, V18D, V18Q, V20L, V20I, V20M, and V20T.
5. The NGF variant of claim 3, wherein the substitutions are selected from the group consisting of F86Y, F86M, F86W, F86S, F86T, T81K, T29V, T29L, T29S, and T81N.
6. The NGF variant of claim 1 selected from the group consisting of NGF130, NGF131 , NGFR2 (NGFrev2), and NGFR3 (NGFrev3).
7. The NGF variant of claim 1, wherein N-terminal amino acids SSSHPIF are absent or substituted with YAEHKS.
8. The NGF variant of claim 1 , further comprising a deletion of amino acid Rl 19 or A 120 or both.
9. The NGF variant of claim 8 further comprising a deletion of amino acid Rl 18.
10. A nucleic acid comprising a nucleotide sequence encoding the NGF variant of claim 1.
11. An expression vector comprising the nucleic acid of claim 10.
12. A host cell comprising the nucleic acid of claim 10.
13. 43 A method of producing an NGF variant, comprising culturing the host cell of claim 12 under conditions that allow expression of the NGF variant*
14. The method of claim 13, further comprising the step of isolating the NGF variant.
15. A composition comprising the NGF variant of claim 1 and a carrier.
16. The NGF variant of claim 1, for use in the preparation of a medicament for treating a neural disorder in a mammal.
17. The NGF variant of claim 16, wherein the neural disorder is peripheral neuropathy.
18. The NGF variant of claim 17, wherein the neural disorder is diabetic peripheral neuropathy.
19. The NGF variant of claim 17, wherein the neural disorder is toxin-induced peripheral neuropathy.
20. The NGF variant of claim 19, wherein the neural disorder is chemotherapy-induced peripheral neuropathy.
21. The NGF variant of claim 17, wherein the peripheral neuropathy is HIV-associated.
22. The NGF variant of claim 17, wherein the peripheral neuropathy affects motoneurons.
23. The NGF variant comprising NGF of claim 1, comprising a substitution at VI 8 and further having substitutions at amino acid positions V20, G23 and H84, and either F86, Y79 or T81, which impart trkC binding, wherein the variant binds trkC. 01202969\45-01 42 132251/4
24. The NGF variant of claim 23, wherein both T81 and F86 are substituted.
25. The NGF variant of claim 23, wherein the substitution of T29 is selected from a T29V, a T29L and a T29S substitution.
26. The NGF variant of claim 23 selected from the group consisting of NGF126, NGF1234, NGF124, NGF125, NGF12, NGFR4 (NGFrev4), NGF123, and NGF127.
27. ' The NGF variant of claim 23, further comprising either an amino acid substitution that imparts trkB binding or a modification that reduces or eliminates trkA binding, or both.
28. A nucleic acid comprising a nucleotide sequence encoding the NGF variant of claim 23.
29. An expression vector comprising the nucleic acid of claim 28.
30. A host cell comprising the nucleic acid of claim 28.
31. A method of producing an NGF variant, comprising culturing the host cell of claim 30 under conditions that allow expression of the NGF variant.
32. The method of claim 31 , further comprising the steps of isolating the NGF variant.
33. A composition comprising the NGF variant of claim 23 and a carrier.
34. The NGF variant of claim 23 for use in the preparation of a medicament for treating a neural disorder in a mammal.
35. The NGF variant of claim 34, wherein the neural disorder is peripheral neuropathy.
36. The NGF variant of claim 35, wherein the neural disorder is diabetic peripheral neuropathy.
37. The NGF variant of claim 35, wherein the neural disorder is toxin-induced peripheral neuropathy.
38. The NGF variant of claim 37, wherein the neural disorder is chemotherapy-induced peripheral neuropathy.
39. The NGF variant of claim 35, wherein the peripheral neuropathy is HIV-associated.
40. The NGF variant of claim 35, wherein the peripheral neuropathy affects motorneurons.
41. Use of the NGF variant of claim 1 for the preparation of a medicament for treating a neural disorder in a mammal.
42. The use of claim 41 , wherein the neural disorder is peripheral neuropathy.
43. The use of claim 42, wherein the neural disorder is diabetic peripheral neuropathy.
44. The use of claim 42, wherein the neural disorder is toxin-induced peripheral neuropathy.
45. The use of claim 44, wherein the neural disorder is chemotherapy-induced peripheral neuropathy.
46. The use of claim 42, wherein the peripheral neuropathy is HIV-associated.
47. The use of claim 42, wherein the peripheral neuropthy affects motorneurons.
48. Use of the NGF variant of claim 23 for the preparation of a medicament for treating a neural disorder in a mammal.
49. The use of claim 48, wherein the neural disorder is peripheral neuropathy.
50. The use of claim 49, wherein the neural disorder is diabetic peripheral neuropathy. 01202969\45-01 43 132251/4
51. The use of claim 49, wherein the neural disorder is toxin-induced peripheral neuropathy.
52. The use of claim 51, wherein the neural disorder is chemotherapy-induced peripheral neuropathy.
53. The use of claim 49, wherein the peripheral neuropathy is HIV-associated.
54. The use of claim 49, wherein the peripheral neuropthy affects motomeurons. For the Applicants, PARTNERS 01202969W5-01 44
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/845,541 US6333310B1 (en) | 1994-06-03 | 1997-04-25 | NGF variants |
| US84104597A | 1997-04-29 | 1997-04-29 | |
| PCT/US1998/008242 WO1998049308A1 (en) | 1997-04-25 | 1998-04-23 | Ngf variants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL132251A true IL132251A (en) | 2009-12-24 |
Family
ID=42113710
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL132251A IL132251A (en) | 1997-04-25 | 1999-10-06 | NGF VARIANTS HAVING AMINO ACID SUBSTITUTIONS THAT IMPART trkC BINDING |
Country Status (1)
| Country | Link |
|---|---|
| IL (1) | IL132251A (en) |
-
1999
- 1999-10-06 IL IL132251A patent/IL132251A/en not_active IP Right Cessation
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