# US 9,518,105 B2 · Polypeptides derived from calcitonin receptors and methods of use

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- Number: US 9,518,105 B2
- Document ID: US9518105B2
- Status: Granted
- Kind: B2
- Application number: 13/992,005
- Filed: 2011-12-07
- Published: 2013-12-26
- Granted: 2016-12-13
- Earliest claimed: 2010-12-08
- Assignees: The Research Foundation for The State University of New York
- Applicants: Srinivas Pentyala
- Inventors: Srinivas Pentyala
- Web page: https://patentgrep.com/patent/US9518105B2

## CPC

- C07K 14/723: {G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- 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: 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

The present invention is based, in part, on our discovery of compositions and methods that can be used to treat a patient who has a compromised bone (due, for example, to a disease such as osteoporosis or an injury such as a bone fracture). The compositions can also be administered prophylactically. For example, they can be administered to help maintain bone health as a patient ages. More specifically, the compositions include polypeptides that constitute (or that include) a fragment of a calcitonin receptor (CR) and polypeptides that constitute (or include) biologically active variants of those fragments. Sequence-specific formulas are provided herein, and polypeptides conforming to those formulas, as well as nucleic acids encoding them, expression vectors, host cells, pharmaceutical formulations, and methods of their preparation and use are within the scope of the present invention.

## Claims

### Claim 1

A method of treating a patient who is at risk for, or who has been diagnosed as having, a compromised bone, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising a substantially pure polypeptide comprising a fragment of a calcitonin receptor, wherein the polypeptide comprises an amino acid sequence conforming to:
(SEQ ID NO:4);
Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp
(SEQ ID NO:5);
Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp
(SEQ ID NO:6);
Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp
or
(SEQ ID NO:7),
Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp
and wherein the polypeptide is 12-18 amino acids in length and is amidated at the C-terminus.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compromised bone comprises cancerous cells.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compromised bone is associated with a bone disorder.

### Claim 4 (depends on 3)

The method of claim 3, wherein the bone disorder is osteoporosis, osteopenia, osteomalacia or rickets.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compromised bone is a fractured bone.

### Claim 6 (depends on 1)

The method of claim 1, wherein the patient is a human patient.

### Claim 7 (depends on 6)

The method of claim 6, wherein the human patient is more than about 50 years old.

### Claim 8 (depends on 1)

The method of claim 1, wherein the polypeptide comprises Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp (SEQ ID NO:4).

### Claim 9 (depends on 1)

The method of claim 1, wherein the polypeptide comprises Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp (SEQ ID NO:5).

### Claim 10 (depends on 1)

The method of claim 1, wherein the polypeptide comprises Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp (SEQ ID NO:6).

### Claim 11 (depends on 1)

The method of claim 1, wherein the polypeptide comprises Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp (SEQ ID NO:7).

### Claim 12 (depends on 6)

The method of claim 6, wherein the polypeptide further comprises, at the amino terminus of the polypeptide: a glutamate (Glu) residue; a pyroglutamate (pGlu) residue; or the amino acid sequence Lys-Arg-Gln.

### Claim 13 (depends on 1)

The method of claim 1, wherein the polypeptide comprises an amino acid sequence conforming to:
(SEQ ID NO:8);
Glu/pG1u-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-
Arg-Trp
(SEQ ID NO:9);
Glu/pG1u-Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-
Arg-Trp
(SEQ ID NO:10);
Glu/pG1u-Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-
Arg-Trp
or
(SEQ ID NO:11)
Glu/pG1u-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-
Arg-Trp.

### Claim 14 (depends on 1)

The method of claim 1, wherein the polypeptide comprises an amino acid sequence conforming to:
Lys-Arg-Gln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp (SEQ ID NO:12);
Lys-Arg-Gln-Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp (SEQ ID NO:13);
Lys-Arg-Gln-Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp (SEQ ID NO:14); or
Lys-Arg-Gln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp (SEQ ID NO:15).

### Claim 15 (depends on 1)

The method of claim 1, wherein the polypeptide consists of an amino acid sequence conforming to:
(SEQ ID NO: 4)
Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 5)
Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 6)
Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp;
(SEQ ID NO: 7)
Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp;
(SEQ ID NO: 8)
Gln/pGln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 9)
Gln/pGln-Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 10)
Gln/pGln-Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp;
(SEQ ID NO: 11)
Gln/pGln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp;
(SEQ ID NO: 12)
Lys-Arg-Gln/pGln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 13)
Lys-Arg-Gln/pGln-Trp-Val-Gln-Phe-Lys-Ile-Gln-Trp-Asn-Gln-Arg-Trp;
(SEQ ID NO: 14)
Lys-Arg-Gln/pGln-Trp-Thr-Gln-Phe-Lys-Ile-Gln-Trp-Ser-Gln-Arg-Trp;
(SEQ ID NO: 15)
Lys-Arg-Gln/pGln-Trp-Ala-Gln-Phe-Lys-Ile-Gln-Trp-Ser-His-Arg-Trp.

### Claim 16 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is formulated for parenteral administration.

### Claim 17 (depends on 16)

The method of claim 16, wherein the parenteral administration is intravenous administration.