# US 7,608,681 B2 · Methods and compositions for prolonging elimination half-times of bioactive compounds

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,608,681 B2
- Document ID: US7608681B2
- Status: Granted
- Kind: B2
- Application number: 10/149,835
- Filed: 2000-12-22
- Published: 2004-12-16
- Granted: 2009-10-27
- Earliest claimed: 1999-12-24
- Assignees: Genentech, Inc.
- Inventors: Mark S. Dennis; Henry B. Lowman; Warren L. DeLano
- Web page: https://patentgrep.com/patent/US7608681B2

## CPC

- C07K 1/047: {Simultaneous synthesis of different peptide species; Peptide libraries}
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/001: {by chemical synthesis}
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/24: against cytokines, lymphokines or interferons
- C07K 16/461: {Igs containing Ig-regions, -domains or -residues form different species}
- 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)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/55: Fab or Fab'
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Peptide ligands having affinity for IgG or for serum albumin are disclosed. Also disclosed are hybrid molecules comprising a peptide ligand domain and an active domain. The active domain may comprise any molecule having utility as a therapeutic or diagnostic agent. The hybrid molecules of the invention may be prepared using any of a number techniques including production in and purification from recombinant organisms transformed or transfected with an isolated nucleic acid encoding the hybrid molecule, or by chemical synthesis of the hybrid. The hybrid molecules have utility as agents to alter the elimination half-times of active domain molecules. Elimination half-time is altered by generating a hybrid molecule of the present invention wherein the peptide ligand has binding affinity for a plasma protein. In a preferred embodiment, a bioactive molecule having a short elimination half-time is incorporated as or into an active domain of the hybrid molecules of the invention, and the binding affinity of the peptide ligand domain prolongs the elimination half-time of the hybrid as compared to that of the bioactive molecule.

## Claims

### Claim 1

A peptide ligand comprising a non-naturally occurring amino acid sequence, wherein the amino acid sequence is Xaai-Cys-Xaaj-Cys-Xaak that binds IgG-Fc, wherein Xaa is any amino acid, Xaai is 0-4 amino acids, Xaaj is Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Leu -Val-Trp (SEQ ID NO:9), and Xaak is 0-5 amino acids.

### Claim 2 (depends on 1)

The peptide ligand of claim 1 wherein Xaaj is Xaa-Xaa-Xaa -Xaa-Gly-Glu-Leu-Val-Trp (SEQ ID NO: 10).

### Claim 3 (depends on 2)

The peptide ligand of claim 2 wherein Xaaj is Xaa1-Xaa2-Xaa3-Xaa4-Gly-Glu-Leu-Val-Trp-Cys (SEQ ID NO: 10) and Xaa1 is Ala, Ser, or Thr, Xaa2 is Trp or Tyr, Xaa3 is His, or Trp, and Xaa4 is Leu or Met.

### Claim 4 (depends on 1, 2)

The peptide ligand of claim 1 or claim 2 comprising the amino acid sequence Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Leu-Val-Trp-Cys -Xaa-Xaa-Xaa-Xaa-Xaa (SEQ ID NO:11) wherein Xaa is any amino acid.

### Claim 5 (depends on 4)

The peptide ligand of claim 4 comprising the amino acid sequence Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-GIy-Glu-Leu-Val-Trp-Cys-Xaa-Xaa-Xaa -Xaa-Xaa (SEQ ID NO: 12).

### Claim 6 (depends on 5)

The peptide ligand of claim 5 comprising the amino acid sequence Xaa1-Xaa2-Xaa3-Xaa4-Cys-Xaa5-Xaa6-Xaa7-Xaa8-Gly-Glu-Leu-Val-Trp-Cys-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13 (SEQ ID NO:13), wherein Xaa5 is Ala, Ser, or Thr, Xaa6 is Trp or Tyr, Xaa7 is His, or Trp, Xaa8 is Leu or Met, and Xaa1-4 and 9-13 are each an amino acid.

### Claim 7 (depends on 6)

The peptide ligand of claim 6 wherein Xaa4 is Ser, Arg, or Asp; Xaa5 is Ala, Ser, or Thr; Xaa6 is Trp or Tyr; Xaa7 is His or Trp; Xaa8 is Leu or Met; and Xaa9 is Glu, Ser, Thr or Val (SEQ ID NO: 14).

### Claim 8 (depends on 1)

The peptide of claim 1 wherein the peptide ligand comprises the amino acid sequence DCAWHLGELVWCT (SEQ ID NO:8).

### Claim 9 (depends on 1)

The peptide ligand of claim 1, wherein the amino acid sequence is cyclized by the presence of disulfide-bonded Cys residues.

### Claim 10 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand is less than 50 amino acid residues.

### Claim 11 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand is less than 40 amino acid residues.

### Claim 12 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand is between 10 and 30 amino acid residues.

### Claim 13 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand has an IC50 for IgG-Fc of less than about 1 μM.

### Claim 14 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand has an IC50 for IgG-Fc of less than about 100 nM.

### Claim 15 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand is non-covalently adsorbed or covalently bound to a macromolecule.

### Claim 16 (depends on 15)

The peptide ligand of claim 15, wherein the macromolecule is a solid support.

### Claim 17 (depends on 1)

The peptide ligand of claim 1, wherein the peptide ligand is labeled with a detectable moiety.