# US 5,705,478 A · Covalently linked .beta. subunits of the glycoprotein hormones as antagonists > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,478 A - Document ID: US5705478A - Status: Granted - Kind: A - Application number: 08/334,628 - Filed: 1994-11-04 - Granted: 1998-01-06 - Earliest claimed: 1989-02-21 - Assignees: Washington University - Inventors: Irving Boime - Web page: https://patentgrep.com/patent/US5705478A ## CPC - C07K 14/59: Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH] - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2319/00: Fusion polypeptide - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The single chain compounds of the invention comprise two .beta. subunits of the glycoprotein hormones, which .beta. subunits are the same or different. These "two-.beta." forms are antagonists of glycoprotein hormone activity. ## Claims ### Claim 1 A glycosylated or nonglycosylated single chain glycoprotein hormone antagonist of the formula .beta.-(linker).sub.n -.beta. wherein each .beta. is independently selected from the group consisting of the glycoprotein hormone .beta. subunits FSH, TSH, LH and CG, n is 0 or 1, and "linker" is a linker moiety; and wherein: the amino acid sequence of said first .beta.-subunit is linked covalently through a C-terminal carboxyl or N-terminal amino group, optionally through said linker moiety, to a C-terminal carboxyl or N-terminal amino group of the amino acid sequence of said second .beta.-subunit, wherein said .beta.-subunits consist of the native amino acid sequences of said hormones or variants of said amino acid sequences. ### Claim 2 (depends on 1) The glycoprotein hormone antagonist of claim 1 wherein the C-terminus of one .beta. subunit is linked covalently, optionally through a linker moiety, to the N-terminus of the other .beta. subunit. ### Claim 3 (depends on 1) The glycoprotein hormone antagonist of claim 1 wherein said protein includes a linker moiety. ### Claim 4 (depends on 1) The single chain glycoprotein hormone antagonist of claim 1 wherein said .beta.-subunits have the same amino acid sequence. ### Claim 5 (depends on 1) The single chain glycoprotein hormone antagonist of claim 1 wherein the .beta.-subunits have different amino acid sequences. ### Claim 6 (depends on 3) The glycoprotein hormone antagonist of claim 3 wherein said linker comprises a complete or partial CTP unit or variant thereof. ### Claim 7 (depends on 3) The glycoprotein hormone antagonist of claim 3 wherein said linker comprises at least two CTP units or variants thereof. ### Claim 8 (depends on 1) A pharmaceutical composition which comprises the glycoprotein hormone antagonist of claim 1 in admixture with a suitable pharmaceutical excipient. ### Claim 9 (depends on 1) The glycoprotein hormone antagonist of claim 1 coupled to solid support. ### Claim 10 (depends on 3) The glycoprotein hormone antagonist of claim 3 wherein said linker comprises an amino acid or peptide. ### Claim 11 (depends on 10) The glycoprotein hormone antagonist of claim 10 wherein said linker is coupled to said .beta.-subunits through peptide bonds.