PROF. CYRIL YARLING BOWERS, M.D.
Medical Practice at Tulane Ave, New Orleans, LA

4935491, Jun 19, 1990

Aug 24, 1987

7/088431

Karl Folkers - Austin TX
Anders Ljungqvist - Austin TX
Dong-Mei Feng - Austin TX
Cyril Y. Bowers - New Orleans LA
Pui-Fun L. Tang - Kowloon, HK
Minoru Kubota - Yotsukaido, JP

Board of Regents, The University of Texas System - Austin TX
The Administrators of the Tulane Educational Fund - New Orleans LA

C07K 706, C07K 720, A61K 3738

530313

The objective of the research was the achievement of antagonists of the luteinizing hormone releasing hormone (LHRH) which would have adequate antagonistic activity to prevent ovulation, and yet would not have a pronounced structural feature to release a histamine, in vivo. Some existing antagonists of LHRH produced edema of the face and extremities in rats. This recent recognition of the edematogenic and anaphylactoid activities of an antagonist of LHRH necessitated new structural changes if such antagonists were to be considered for potential use as contraceptive agents in the human. Consequently, 57 peptides have been designed, synthesized and bioassayed toward achieving a potent antagonist which releases negligible histamine. Since there was no predictable structural sequence which offered assurance of such achievement, it was necessary to design, synthesize and bioassay a very large number of peptides having diverse structural changes toward ultimately discovering an antagonist with the necessary potency of antiovulatory activity and the necessary negligible release of histamine. Ultimately, this objective was achieved, and this application describes the diverse and unpredictable many positive steps which finally led to the objectives.

4410512, Oct 18, 1983

Dec 28, 1981

6/334488

Cyril Y. Bowers - New Orleans LA

Beckman Instruments, Inc. - Fullerton CA

A61K 3702

424177

Novel combinations comprising (a) at least one peptide having the following amino acid sequence ##STR1## wherein X. sub. 1, X. sub. 2, and X. sub. 3 are selected from a group consisting of N-terminal and desamino alpha-carbon substitutions and a and b are 0 or 1, provided that a and b are always 0 when A. sub. 1 is a desamino residue; A. sub. 1 and A. sub. 4 are selected from a group consisting of histidyl, arginyl, lysyl,. alpha. -naphthylalanyl,. beta. -naphthylalanyl, isoquinolyl, tyrosyl, tryptophyl, phenylalanyl, homologues and anlogues thereof, and, with respect to A. sub. 1 only the desamino forms thereof; A. sub. 2 and A. sub. 5 are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-. alpha. -naphthylalanyl, D-. beta. -naphthylalanyl, D-isoquinolyl, D-tyrosyl, D-tryptophyl, D-phenyalanyl, homologues and analogues thereof; A. sub.

5776901, Jul 7, 1998

Aug 20, 1992

7/932494

Cyril Y. Bowers - New Orleans LA
David Coy - New Orleans LA

Administrators of the Tulane Educational Fund - New Orleans LA

A61K 3800, C07K 500, C07K 700

514 16

Novel peptides of the formula A. sub. 1 -A. sub. 2 -C. sub. 1 -C. sub. 2 -C. sub. 3 -A. sub. 5 are disclosed which promote the release of growth hormone when administered to animals. These peptides can be used therapeutically.

4656247, Apr 7, 1987

Apr 26, 1985

6/727710

Karl Folkers - Austin TX
Xu Jie-Cheng - Shanghai, CN
Cyril Y. Bowers - New Orleans LA

Board of Regents, The University of Texas System - Austin TX

C07K 720

530313

Two sets of hormonal peptides are synthesized which are super agonists of the lutenizing hormone releasing hormone (LHRH). Chronic administration results in the inhibition of LHRH which is responsible for stimulating cell growth in the testes. One peptide has the D(dextro)-form of a mono-heterocyclic amino acid in position six (D-3-pyridyl-alanine) while the other peptide has a bi-heterocyclic amino acid in that same position (. beta. -(3-quinolyl)-D-. alpha. -alanine. Both peptides are less metabolically reactive than those in the prior art and yet both peptides are significantly more potent than LHRH itself.

5470947, Nov 28, 1995

Jun 26, 1989

7/371552

Karl A. Folkers - Austin TX
Anders Ljungqvist - Austin TX
Dong-Mei Feng - Austin TX
Minoru Kubota - Yotsukaido, JP
Pui-Fun L. Tang - Hong Kong, HK
Cyril Y. Bowers - New Orleans LA

Board of Regents, The University of Texas System - Austin TX
The Administrators of the Tulane Educational Fund - New Orleans LA

C07K 723

530313

Antide is the decapeptide, N--Ac--D--2--Nal,D--pClPhe, D--3--Pal, Ser,NicLys, D--NicLys, Leu, ILys, Pro, D--Ala,NH. sub. 2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N--Ac--D--2--Nal, D--pClPhe,D--3--Pal,Ser,PicLys,cis--DpzACAla, Leu,ILys,pro,D--Ala--NH. sub. 2 was one of the most potent and had higher antiovulatory activity than Antide, i. e. 73%/0. 25 ug and 100%/0. 5 ug vs. 36%/0.

4504414, Mar 12, 1985

Mar 28, 1983

6/479645

Karl Folkers - Austin TX
Cyril Y. Bowers - New Orleans LA
Teresa M. Kubiak - New York NY
Janusz Stepinski - Austin TX

Board of Regents, The University of Texas System - Austin TX

C07C10352

2601125LH

Pyridyl-alanyl decapeptides have been effectively synthesized and found to have antiovulatory activity. The exemplary [N-Ac-D-2-Nal. sup. 1,pCl-D-Phe. sup. 2, D-3-Pal. sup. 3,D-Arg. sup. 6,D-Ala. sup. 10 ]-LHRH has very high potency to inhibit ovulation, both parenterally and orally. Also, this exemplary pyridyl-alanyl-decapeptide showed an unexpected prolonged duration of antiovulatory activity. Such pyridyl-alanyl-decapeptides are useful to control reproduction.

5486505, Jan 23, 1996

Oct 16, 1992

7/962069

Cyril Y. Bowers - New Orleans LA
Wayne L. Cody - Saline MI
John C. Hubbs - Kingsport TN
Charles H. Foster - Kingsport TN
Frank A. Momany - Wellesley MA

Polygen Holding Corporation - Wilmington DE

A61K 3800, C07K 706

514 16

Novel polypeptides which promote the release of growth hormone when administered to animals are described. These polypeptides have the formula: A. sub. 1 --D. sup. beta. Nal--A. sub. 3 --Trp--A. sub. 5 --A. sub. 6 --Z wherein A. sub. 1, A. sub. 3, A. sub. 5, A. sub. 6 and Z" are as defined in the specification.

4880778, Nov 14, 1989

Apr 10, 1987

7/037275

Cyril Y. Bowers - New Orleans LA
Frank A. Momany - Concord MA
Ching H. Chang - Kingsport TN
Wayne Cody - Kingsport TN
John C. Hubbs - Gray TN
Charles H. Foster - Kingsport TN

Eastman Kodak Company - Rochester NY

H61K 3743

514 12

Disclosed are combinations of polypeptides acting in a synergistic manner to promote release and elevation of growth hormone levels in the blood of animals. Also disclosed are methods of promoting the release and elevation of growth hormone levels in the blood of animals using the disclosed combination of polypeptides.

5763404, Jun 9, 1998

Jun 6, 1995

8/466333

Karl A. Folkers - Austin TX
Cyril Y. Bowers - New Orleans LA
Anders Ljungqvist - Austin TX
Pui-Fun Louisa Tang - Kornhill, Quarry Bay, Hong Kong, HK
Minoru Kubota - Yotsukaido-shi, Chiba 284, JP
Dong-Mei Feng - Lansdale PA

A61K 3824, A61K 3804, C07K 723

514 15

Antide is the decapeptide, N-Ac-D-2-Nal,D-pClPhe, D-3-Pal, Ser,NicLys, D-NicLys, Leu, ILys, Pro, D-Ala,NH. sub. 2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N-Ac-D-2-Nal, D-pClPhe,D-3-Pal,Ser,PicLys,cis-DPzACAla,Leu,ILys,Pro,D-Ala-NH. sub. 2 was one of the most potent and had higher antiovulatory activity than Antide, i. e. 73%/0. 25 ug and 100%/0. 5 ug vs. 36%/0. 5 ug and 100%/1. 0 ug.

5656727, Aug 12, 1997

Apr 28, 1995

8/430602

Cyril Y. Bowers - New Orleans LA
Karl A. Folkers - Austin TX
Anna Janecka - Lodz, PL

The Administrators of the Tulane Educational Fund - New Orleans LA
Board of Regents, The University of Texas System - Austin TX

C07K 700, C07K 706, A61K 3800

530328

LHRH analogs and congeners with high water solubility have been synthesized. These new analogs had 0%-100% antiovulatory activity at a 0. 5. mu. g dosage and 0%-80% at 0. 25. mu. g. The ED. sub. 50 for histamine release was 30. 5. mu. g/ml->300. mu. g/ml.