# US 10,307,455 B2 · Activin type 2 receptor antibodies

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- Number: US 10,307,455 B2
- Document ID: US10307455B2
- Status: Granted
- Kind: B2
- Application number: 15/456,392
- Filed: 2017-03-10
- Published: 2017-10-05
- Granted: 2019-06-04
- Earliest claimed: 2016-03-10
- Assignees: Acceleron Pharma Inc.; Adimab, LLC
- Applicants: Acceleron Pharma Inc.; Adimab, LLC
- Inventors: Ravindra Kumar; Jonathan Belk; Asya Grinberg; Dianne Sako; Roselyne Castonguay
- Web page: https://patentgrep.com/patent/US10307455B2

## CPC

- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/10: for osteoporosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 14/001: {by chemical synthesis}
- C07K 14/47: from mammals
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- 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 5/00: Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K 2317/21: from primates, e.g. man
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- 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
- 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
- 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)

## Abstract

This disclosure provides ActRII-binding proteins such as anti-ActRIIA and anti-ActRIIB antibodies, and compositions and methods for making the ActRII-binding proteins. In certain aspects the ActRII-binding proteins inhibit, or antagonize ActRII activity. In addition, the disclosure provides compositions and methods for diagnosing and treating diseases and conditions associated muscle wasting; a fibrotic condition; an inflammatory, cardiovascular, pulmonary, musculoskeletal, neurologic, ocular, skeletal, autoimmune, or metabolic disease or condition; wound healing; and cancer, and other ActRII-mediated diseases and conditions.

## Claims

### Claim 1

An ActRII-binding antibody comprising a set of CDRs in which:
(a) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO:166;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO:167;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO:168;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO:173;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:174; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:175;
and wherein the antibody binds ActRIIB;
(b) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 3 or 17;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 4 or 18;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(c) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 64 or 78;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 65 or 79;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 66 or 80;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 71;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 72; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:73;
and wherein the antibody binds ActRIIB;
(d) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 3 or 58;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 4 or 59;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 46;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 51;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 52; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 53;
and wherein the antibody binds ActRIIB;
(e) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 145;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 146;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 147;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 152;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 153; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 154;
and wherein the antibody binds ActRIIB;
(f) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(g) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 126;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 127;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 128;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 133;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 134; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 135;
and wherein the antibody binds ActRIIA;
h) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 3 or 17;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 24 or 30;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5:
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(i) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 3 or 17;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 36;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(j) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 23 or 29;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 4 or 18;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(k) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 23 or 29;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 24 or 30;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(l) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 23 or 29;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 36;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB:
(m) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 35 or 41;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 4 or 18;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB:
(n) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 35 or 41;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 24 or 30;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(o) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 35 or 41;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 36;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 5;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 10;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 11; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 12;
and wherein the antibody binds ActRIIB;
(p) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(g) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(r) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(s) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(t) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(u) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(v) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(w) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 85 or 99;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(x) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(y) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(z) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 86 or 100;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(aa) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(bb) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(cc) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 107 or 114;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(dd) (i) VH-CDRI has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 87 or 101;
(iv) VL-CDRI has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(ee) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 108 or 115;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA;
(ff) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO: 106 or 113;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO: 120;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO: 121;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO: 92;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO: 93; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO: 94;
and wherein the antibody binds ActRIIB and ActRIIA.

### Claim 2 (depends on 1)

The ActRII-binding antibody of claim 1, which comprises a VH and a VL pair selected from:
(a) a VH sequence of SEQ ID NO:165 and a VL sequence of SEQ ID NO:172;
(b) a VH sequence of SEQ ID NO:2 and a VL sequence of SEQ ID NO:9;
(c) a VH sequence of SEQ ID NO:16 and a VL sequence of SEQ ID NO:9;
(d) a VH sequence of SEQ ID NO:22 and a VL sequence of SEQ ID NO:9;
(e) a VH sequence of SEQ ID NO:28 and a VL sequence of SEQ ID NO:9;
(f) a VH sequence of SEQ ID NO:34 and a VL sequence of SEQ ID NO:9;
(g) a VH sequence of SEQ ID NO:40 and a VL sequence of SEQ ID NO:9;
(h) a VH sequence of SEQ ID NO:45 and a VL sequence of SEQ ID NO:50;
(i) a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:50;
(j) a VH sequence of SEQ ID NO:63 and a VL sequence of SEQ ID NO:70;
(k) a VH sequence of SEQ ID NO:77 and a VL sequence of SEQ ID NO:70;
(l) a VH sequence of SEQ ID NO:144 and a VL sequence of SEQ ID NO:151;
(m) a VH sequence of SEQ ID NO:84 and a VL sequence of SEQ ID NO:91;
(n) a VH sequence of SEQ ID NO:98 and a VL sequence of SEQ ID NO:91;
(o) a VH sequence of SEQ ID NO:105 and a VL sequence of SEQ ID NO:91;
(p) a VH sequence of SEQ ID NO:112 and a VL sequence of SEQ ID NO:91;
(q) a VH sequence of SEQ ID NO:119 and a sequence of SEQ ID NO:91; and
(r) a VH sequence of SEQ ID NO:125 and a sequence of SEQ ID NO:132.

### Claim 3 (depends on 1)

The ActRII-binding antibody of claim 1, wherein the antibody has at least one characteristic selected from:
(a) competing with activin A, activin B, BMP7, BMP9, BMP10, GDF8 (myostatin), GDF11, or Nodal, for binding to ActRIIB or ActRIIA;
(b) decreasing the phosphorylation of one or more Smads in cells expressing ActRIIB and/or ActRIIA in the presence of an ActRIIB or ActRIIA ligand;
(c) decreasing the phosphorylation of ALK4 or ALK7 in cells expressing ActRIIB or ActRIIA and ALK4 or ALK7 in the presence of an ActRIIB or ActRIIA ligand; and
(d) binding to ActRIIB or ActRIIA with a KD of ≤1 nM and ≥1 pM, as determined by BIACORE® analysis.

### Claim 4 (depends on 1)

The ActRII-binding antibody of claim 1, wherein the antibody is a monoclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, a bi-specific antibody, a multi-specific antibody, or an ActRII-binding antibody fragment.

### Claim 5 (depends on 4)

The ActRII-binding antibody of claim 4, wherein the ActRII-binding antibody fragment is selected from a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, or a single chain antibody molecule.

### Claim 6 (depends on 4)

The ActRII-binding antibody of claim 4, wherein the antibody further comprises a heavy chain immunoglobulin constant domain selected from:
(a) a human IgA constant domain;
(b) a human IgD constant domain;
(c) a human IgE constant domain;
(d) a human IgG1 constant domain;
(e) a human IgG2 constant domain;
(f) a human IgG3 constant domain;
(g) a human IgG4 constant domain; and
(h) a human IgM constant domain.

### Claim 7 (depends on 4)

The ActRII-binding antibody of claim 4, wherein the antibody further comprises a light chain immunoglobulin constant domain selected from:
(a) a human Ig kappa constant domain; and
(b) a human Ig lambda constant domain.

### Claim 8 (depends on 4)

The ActRII-binding antibody of claim 4, wherein the antibody further comprises a human IgG1 heavy chain constant domain and a human lambda light chain constant domain.

### Claim 9 (depends on 1)

An isolated nucleic acid molecule or a set of nucleic acid molecules that encodes the ActRII-binding antibody of claim 1.

### Claim 10 (depends on 9)

A vector comprising the nucleic acid molecule or the set of nucleic acid molecules according to claim 9.

### Claim 11 (depends on 9)

A host cell comprising the nucleic acid molecule or the set of nucleic acid molecules according to claim 9.

### Claim 12 (depends on 11)

A method of making an ActRII-binding antibody, said method comprising culturing the host cell according to claim 11 under suitable conditions for producing the ActRII-binding antibody.

### Claim 13 (depends on 12)

An ActRII-binding antibody produced using the method of claim 12.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising the ActRII-binding antibody according to claim 1 and a pharmaceutically acceptable carrier.