Compositions and methods for treatment of bone associated diseases

Patent metadata

Field	Value
Publication number	US-11098091-B2
Application number	US-201716326456-A
Country	US
Kind code	B2
Filing date	Aug 17, 2017
Priority date	Aug 18, 2016
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

Mutant M-CSF protein, comprising αvβ3 integrin binding motif and pharmaceutical compositions comprising same, are provided. Further, use of the composition for the treatment and or prevention of diseases associated with increased bone resorption are provided.

First claim

What is claimed is:

1. A polypeptide comprising an amino acid sequence that differs from the amino acid sequence of SEQ ID NO: 1, by (a): having a Cysteine to Serine substitution in position 31; wherein said polypeptide is characterized by: having reduced homodimerization capability, strong binding specificity to c-FMS; and osteoclast differentiation inducing activity: or by (b): having a Cysteine to Serine substitution in position 31 and a Methionine to Arginine substitution in position 27; wherein said polypeptide is characterized by: diminished non-covalent dimerization, antagonizing c-FMS and impairing osteoclast differentiation.

2. An isolated nucleic acid molecule encoding the polypeptide of claim 1 .

3. An expression vector comprising the nucleic acid of claim 2 .

4. A cell transformed or transfected with the expression vector of claim 3 .

5. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutical acceptable carrier.

6. A method for treating a disease characterized by excessive osteoclast differentiation or increased bone resorption in a subject in need thereof, the method comprising the step of administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising a polypeptide and a pharmaceutically acceptable carrier, thereby treating said disease in a subject in need thereof, wherein the polypeptide comprises an amino acid sequence that differs from the amino acid sequence of SEQ ID NO: 1 by having a Cysteine to Serine substitution in position 31 and a Methionine to Arginine substitution in position 27; wherein said polypeptide is characterized by diminished non-covalent dimerization, antagonizing c-FMS and impairing osteoclast differentiation.

7. The method of claim 6 , wherein said disease associate with increased bone resorption is osteoporosis.

Assignees

• Nat Inst Biotechnology Negev Ltd
• B G Negev Technologies And Applications Ltd At Ben Gurion Univ

Inventors

• Papo Niv
• Levaot Noam
• Zur Yuval
• Rosenfeld Lior

Classifications

• C07K14/52

  Cytokines; Lymphokines; Interferons · CPC title

• A61K38/19 Primary

  Cytokines; Lymphokines; Interferons · CPC title

• C07K14/53

  Colony-stimulating factor [CSF] · CPC title

• A61K38/00

  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) · CPC title

• C07K14/535

  Granulocyte CSF; Granulocyte-macrophage CSF · CPC title