ANTI-MYOSTATIN ANTIBODIES, POLYPEPTIDES CONTAINING VARIANT FC REGIONS, AND METHODS OF USE
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Abstract
The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.
8 Citations
107 Claims
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1-13. -13. (canceled)
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14. A method of blocking release of mature myostatin from latent myostatin in a biological sample comprising contacting a biological sample containing latent myostatin with an antibody that binds latent myostatin under conditions permissive for binding of the antibody to the latent myostatin, and blocking release of mature myostatin from the latent myostatin;
- wherein the antibody comprises;
(a) a HVR-H1 comprising the amino acid sequence X1X2DIS (SEQ ID NO;
126), wherein X1 is S or H, X2 is Y, T, D or E;(b) a HVR-H2 comprising the amino acid sequence IISX1AGX2X3YX4X5X6WAKX7 (SEQ ID NO;
127), wherein X1 is Y or H, X2 is S or K, X3 is T, M or K, X4 is Y or K, X5 is A, M or E, X6 is S or E, X7 is G or K;(c) a HVR-H3 comprising the amino acid sequence GVPAX1SX2GGDX3 (SEQ ID NO;
128), wherein X1 is Y or H, X2 is T or H, X3 is L or K;(d) a HVR-L1 comprising the amino acid sequence X1X2SQX3VX4X5X6NWLS (SEQ ID NO;
129), wherein X1 is Q or T, X2 is S or T, X3 is S or E, X4 is Y or F, X5 is D or H, X6 is N, D, A or E;(e) a HVR-L2 comprising the amino acid sequence WAX1TLAX2 (SEQ ID NO;
130), wherein X1 is S or E, X2 is S, Y, F or W; and(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX1YA (SEQ ID NO;
131), wherein X1 is L or R. - View Dependent Claims (55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
- wherein the antibody comprises;
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15. A method of reducing the concentration of latent myostatin in a biological sample comprising contacting a biological sample containing latent myostatin with an antibody that binds latent myostatin under conditions permissive for binding of the antibody to the latent myostatin, and removing the complex formed between the antibody and the latent myostatin;
- wherein the antibody comprises;
(a) a HVR-H1 comprising the amino acid sequence X1X2DIS (SEQ ID NO;
126), wherein X1 is S or H, X2 is Y, T, D or E;(b) a HVR-H2 comprising the amino acid sequence IISX1AGX2X3YX4X5X6WAKX7 (SEQ ID NO;
127), wherein X1 is Y or H, X2 is S or K, X3 is T, M or K, X4 is Y or K, X5 is A, M or E, X6 is S or E, X7 is G or K;(c) a HVR-H3 comprising the amino acid sequence GVPAX1SX2GGDX3 (SEQ ID NO;
128), wherein X1 is Y or H, X2 is T or H, X3 is L or K;(d) a HVR-L1 comprising the amino acid sequence X1X2SQX3VX4X5X6NWLS (SEQ ID NO;
129), wherein X1 is Q or T, X2 is S or T, X3 is S or E, X4 is Y or F, X5 is D or H, X6 is N, D, A or E;(e) a HVR-L2 comprising the amino acid sequence WAX1TLAX2 (SEQ ID NO;
130), wherein X1 is S or E, X2 is S, Y, F or W; and(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX1YA (SEQ ID NO;
131), wherein X1 is L or R. - View Dependent Claims (65, 66, 67, 68, 69, 70, 71, 72, 73, 74)
- wherein the antibody comprises;
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16. (canceled)
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17. A method of treating an individual having a muscle wasting disease comprising administering to the individual an effective amount of an antibody that binds latent myostatin;
- wherein the antibody comprises;
(a) a HVR-H1 comprising the amino acid sequence X1X2DIS (SEQ ID NO;
126), wherein X1 is S or H, X2 is Y, T, D or E;(b) a HVR-H2 comprising the amino acid sequence IISX1AGX2X3YX4X5X6WAKX7 (SEQ ID NO;
127), wherein X1 is Y or H, X2 is S or K, X3 is T, M or K, X4 is Y or K, X5 is A, M or E, X6 is S or E, X7 is G or K;(c) a HVR-H3 comprising the amino acid sequence GVPAX1SX2GGDX3 (SEQ ID NO;
128), wherein X1 is Y or H, X2 is T or H, X3 is L or K;(d) a HVR-L1 comprising the amino acid sequence X1X2SQX3VX4X5X6NWLS (SEQ ID NO;
129), wherein X1 is Q or T, X2 is S or T, X3 is S or E, X4 is Y or F, X5 is D or H, X6 is N, D, A or E;(e) a HVR-L2 comprising the amino acid sequence WAX1TLAX2 (SEQ ID NO;
130), wherein X1 is S or E, X2 is S, Y, F or W; and(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX1YA (SEQ ID NO;
131), wherein X1 is L or R. - View Dependent Claims (75, 76, 77, 78, 79, 80, 81, 82, 83, 84)
- wherein the antibody comprises;
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18. A method of increasing at least one of mass of muscle tissue and strength of muscle tissue in an individual comprising administering to the individual an effective amount of an antibody that binds latent myostatin to increase at least one of mass of muscle tissue and strength of muscle tissue;
- wherein the antibody comprises;
(a) a HVR-H1 comprising the amino acid sequence X1X2DIS (SEQ ID NO;
126), wherein X1 is S or H, X2 is Y, T, D or E;(b) a HVR-H2 comprising the amino acid sequence IISX1AGX2X3YX4X5X6WAKX7 (SEQ ID NO;
127), wherein X1 is Y or H, X2 is S or K, X3 is T, M or K, X4 is Y or K, X5 is A, M or E, X6 is S or E, X7 is G or K;(c) a HVR-H3 comprising the amino acid sequence GVPAX1SX2GGDX3 (SEQ ID NO;
128), wherein X1 is Y or H, X2 is T or H, X3 is L or K;(d) a HVR-L1 comprising the amino acid sequence X1X2SQX3VX4X5X6NWLS (SEQ ID NO;
129), wherein X1 is Q or T, X2 is S or T, X3 is S or E, X4 is Y or F, X5 is D or H, X6 is N, D, A or E;(e) a HVR-L2 comprising the amino acid sequence WAX1TLAX2 (SEQ ID NO;
130), wherein X1 is S or E, X2 is S, Y, F or W; and(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX1YA (SEQ ID NO;
131), wherein X1 is L or R. - View Dependent Claims (85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97)
- wherein the antibody comprises;
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19. (canceled)
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20. A method of reducing body fat accumulation in an individual comprising administering to the individual an effective amount of an antibody that binds latent myostatin to reduce body fat accumulation;
- wherein the antibody comprises;
(a) a HVR-H1 comprising the amino acid sequence X1X2DIS (SEQ ID NO;
126), wherein X1 is S or H, X2 is Y, T, D or E;(b) a HVR-H2 comprising the amino acid sequence IISX1AGX2X3YX4X5X6WAKX7 (SEQ ID NO;
127), wherein X1 is Y or H, X2 is S or K, X3 is T, M or K, X4 is Y or K, X5 is A, M or E, X6 is S or E, X7 is G or K;(c) a HVR-H3 comprising the amino acid sequence GVPAX1SX2GGDX3 (SEQ ID NO;
128), wherein X1 is Y or H, X2 is T or H, X3 is L or K;(d) a HVR-L1 comprising the amino acid sequence X1X2SQX3VX4X5X6NWLS (SEQ ID NO;
129), wherein X1 is Q or T, X2 is S or T, X3 is S or E, X4 is Y or F, X5 is D or H, X6 is N, D, A or E;(e) a HVR-L2 comprising the amino acid sequence WAX1TLAX2 (SEQ ID NO;
130), wherein X1 is S or E, X2 is S, Y, F or W; and(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX1YA (SEQ ID NO;
131), wherein X1 is L or R. - View Dependent Claims (98, 99, 100, 101, 102, 103, 104, 105, 106, 107)
- wherein the antibody comprises;
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21-54. -54. (canceled)
Specification