Claims
- 1. Water soluble mammalian neutral endopeptidase which is free of detergent, wherein said neutral endopeptidase is encoded by a DNA selected from the group consisting of:
- a) a rat DNA sequence encoding neutral endopeptidase,
- b) a human DNA sequence encoding neutral endopeptidase, and
- c) a DNA sequence which hybridizes to a) or b) and which encodes a mammalian neutral endopeptidase.
- 2. A non-naturally occurring neutral endopeptidase wherein a predetermined amino acid residue is substituted, inserted or deleted, wherein said variant neutral endopeptidase is encoded by a DNA which hybridizes to a rat DNA sequence encoding neutral endopeptidase or a human DNA sequence encoding neutral endopeptidase.
- 3. The neutral endopeptidase of claim 2 that is human neutral endopeptidase.
- 4. The neutral endopeptidase of claim 2 which cleaves the Gly-Trp or Gly-Tyr amide bond of the substrates dansyl-Gly-Trp-Gly or dansyl-Gly-Tyr-Gly.
- 5. Transmembrane domain-deleted mammalian neutral endopeptidase, wherein said transmembrane domain-deleted neutral endopeptidase is encoded by a DNA which will hybridize to a DNA sequence selected from the group consisting of:
- a) a rat DNA sequence encoding neutral endopeptidase; and
- b) a human DNA sequence encoding neutral endopeptidase.
- 6. Cytoplasmic domain-deleted mammalian neutral endopeptidase, wherein said cytoplasmic domain-deleted neutral endopeptidase is encoded by a DNA which will hybridize to a DNA sequence selected from the group consisting of:
- a) a rat DNA sequence encoding neutral endopeptidase, and
- b) a human DNA sequence encoding neutral endopeptidase.
- 7. Mammalian neutral endopeptidase according to claim 6 wherein the transmembrane domain is also deleted.
- 8. Human transmembrane domain-deleted neutral endopeptidase wherein said human transmembrane domain-deleted neutral endopeptidase is encoded by a DNA which will hybridize to a human DNA sequence encoding neutral endopeptidase.
- 9. The human neutral endopeptidase of claim 8 wherein the cytoplasmic domain is also deleted.
- 10. A neutral endopeptidase encoded by a DNA which hybridizes to a rat DNA sequence encoding neutral endopeptidase or a human DNA sequence encoding neutral endopeptidase and which encodes a mammalian neutral endopeptidase containing a deletion, insertion or substitution in the cytoplasmic domain.
- 11. A neutral endopeptidase encoded by a DNA which hybridizes to a rat DNA sequence encoding neutral endopeptidase or a human DNA sequence encoding neutral endopeptidase and which encodes a mammalian neutral endopeptidase containing a deletion, insertion or substitution in the transmembrane domain.
- 12. A pharmaceutical preparation useful for therapeutic treatment of endogenous peptide-mediated disorders or diseases comprising a therapeutically effective amount of neutral endopeptidase and a pharmaceutically acceptable carrier, wherein said neutral endopeptidase is encoded by a DNA selected from the group consisting of:
- a) a rat DNA sequence encoding neutral endopeptidase,
- b) a human DNA sequence encoding neutral endopeptidase, and
- c) a DNA sequence which hybridizes to a) or b) and which encodes a mammalian neutral endopeptidase.
- 13. The preparation of claim 12 which is sterile.
- 14. The preparation of claim 12 wherein the neutral endopeptidase is transmembrane domain-deleted neutral endopeptidase.
- 15. The pharmaceutical composition according to claim 12 wherein said neutral endopeptidase is human neutral endopeptidase.
- 16. The preparation of claim 12 wherein the neutral endopeptidase is cytoplasmic domain-deleted neutral endopeptidase.
- 17. The preparation of claim 16 wherein the carrier is a salve for epidermal application.
- 18. The pharmaceutical composition of claim 12 wherein both the amino terminal transmembrane domain and the cytoplasmic domain of said neutral endopeptidase are deleted.
- 19. The pharmaceutical composition according to claim 18 wherein said neutral endopeptidase is human neutral endopeptidase.
- 20. A composition comprising mammalian neutral endopeptidase unaccompanied by associated native glycosylation and which is free of glycosylated mammalian neutral endopeptidase, wherein said neutral endopeptidase is encoded by a DNA selected from the group consisting of:
- a) a rat DNA sequence encoding neutral endopeptidase,
- b) a human DNA sequence encoding neutral endopeptidase, and
- c) a DNA sequence which hybridizes to a) or b) and which encodes a mammalian neutral endopeptidase.
Parent Case Info
This is a continuing application of U.S. Ser. No. 07/540,439, filed Jun. 19, 1990, now abandoned, which is a continuing application of U.S. Ser. No. 07/002,478, filed Jan. 12, 1987, now U.S. Pat. No. 4,960,700, which is a continuing application of U.S. Ser. No. 06/946,566, filed Dec. 24, 1986, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5262178 |
Malfroy-Camine et al. |
Nov 1993 |
|
Non-Patent Literature Citations (9)
Entry |
Malfroy et. al. (1984) J. Biol. Chem. 259, 14365-14370. |
Gafford et. al. (1983) Biochem. 22, 3265-3271. |
Kalyan et. al. (1983) J. Biol. Chem. 258, 67-74. |
Almenoff et al., Biochemistry 22:590-599 (1983). |
Tonouchi et al., Nucleic Acids Res. 14:7557-7568 (1986). |
Treiger et al., J. Immunol. 136:4099-4105 (1986). |
Skidgel et al., Peptides 5:769-776 (1984). |
Bleecker et al., Amer. J. Med. 81(5A):93-102 (1986). |
Kerr, M.A., et al., "The Purification and Specificity of a Neutral Endopeptidase from Rabbit Kidney Brush Border." Biochem. J., 137:477-488 (1974). |
Continuations (2)
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Number |
Date |
Country |
Parent |
540439 |
Jun 1990 |
|
Parent |
02478 |
Jan 1987 |
|
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
946566 |
Dec 1986 |
|