# US 10,370,424 B2 · Designer osteogenic proteins

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- Number: US 10,370,424 B2
- Document ID: US10370424B2
- Status: Granted
- Kind: B2
- Application number: 15/820,527
- Filed: 2017-11-22
- Published: 2018-03-15
- Granted: 2019-08-06
- Earliest claimed: 2010-08-20
- Assignees: Wyeth
- Applicants: Wyeth LLC
- Inventors: John Wozney; Howard Seeherman; Christopher Todd Brown
- Web page: https://patentgrep.com/patent/US10370424B2

## CPC

- C07K 14/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- C12N 15/09: Recombinant DNA-technology
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.

## Claims

### Claim 1

A composition comprising a designer bone morphogenetic protein (BMP) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO:15 and a carrier.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the designer BMP has a binding profile which includes at least one of the following: binding to the Activin receptor-Like Kinase 2(ALK2) receptor with a KD not greater than about 2 nM; binding to the Activin receptor-Like Kinase 3ALK3) receptor with a KD not greater than about 2 nM; binding to the Activin receptor-Like Kinase 6(ALK6) receptor with a KD not greater than about 1 nM; binding to the Activin type IIA Receptor (ActRIIA) with a KD not greater than about 2 nM; binding to the Activin type IIB Receptor (ActRIIB) with a KD not greater than about 0.5 nM; and binding to the BMP type IIA Receptor (BMPRIIA) with a KD not greater than about 3.5 nM.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 8.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 9.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 10.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 11.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 12.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 13.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 14.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the designer BMP comprises the amino acid sequence of SEQ ID NO: 15.

### Claim 11 (depends on 1)

A kit comprising one or more composition of claim 1.

### Claim 12

A kit comprising a designer bone morphogenetic protein (BMP) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15 and combinations thereof.

### Claim 13 (depends on 12)

The kit of claim 12, further comprising a fluid for diluting the designer BMP.
