# US 9,573,995 B2 · Compositions and methods for growth factor modulation

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- Number: US 9,573,995 B2
- Document ID: US9573995B2
- Status: Granted
- Kind: B2
- Application number: 14/795,007
- Filed: 2015-07-09
- Published: 2015-12-17
- Granted: 2017-02-21
- Earliest claimed: 2013-05-06
- Assignees: Scholar Rock, Inc.
- Applicants: Scholar Rock, Inc.
- Inventors: Thomas Schurpf; Nagesh K. Mahanthappa; Michelle Marie Straub
- Web page: https://patentgrep.com/patent/US9573995B2

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 39/001134: {Transforming growth factor [TGF]}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/495: Transforming growth factor [TGF]
- C07K 16/005: {constructed by phage libraries}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C12N 15/1037: {Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display}
- 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 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- G01N 2333/495: Transforming growth factor [TGF]
- G01N 2333/71: for growth factors; for growth regulators
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF-β superfamily of proteins.

## Claims

### Claim 1

An antibody that binds to a protein complex, said protein complex comprising:
a. glycoprotein-A repetitions predominant protein (GARP) comprising the amino acid sequence of SEQ ID NO: 159, and
b. a growth factor prodomain complex (GPC) comprising human TGF-β1 growth factor and human TGF-β1 LAP;
wherein said antibody binds a GARP epitope of the protein complex, but does not bind free GARP.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein said antibody is a TGF-β1 inhibiting antibody.

### Claim 3 (depends on 2)

The inhibiting antibody of claim 2, wherein said inhibiting antibody is a humanized antibody.

### Claim 4 (depends on 2)

The inhibiting antibody of claim 2, wherein said inhibiting antibody is a monoclonal antibody.

### Claim 5 (depends on 2)

The inhibiting antibody of claim 2, wherein said inhibiting antibody is a multispecific antibody.

### Claim 6 (depends on 5)

The multispecific antibody of claim 5 comprising a bispecific antibody.

### Claim 7 (depends on 2)

The inhibiting antibody of claim 2, wherein said inhibiting antibody is an antibody fragment.

### Claim 8 (depends on 7)

The inhibiting antibody of claim 7, wherein said antibody fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, a Fv fragment, a diabody, a linear antibody, and a single-chain antibody molecule.

### Claim 9 (depends on 2)

The inhibiting antibody of claim 2 comprising an antibody mimetic.

### Claim 10 (depends on 9)

The inhibiting antibody of claim 9, wherein the antibody mimetic is selected from the group consisting of a monobody, an affibody, an affilin, an affitin, an anticalin, an avimer, a centyrin, a darpin, and a fynomer.