ActRII receptor polypeptides, methods and compositions
AssigneeAcceleron Pharma Inc.
InventorsJohn Knopf, Jasbir Seehra
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Abstract
In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, and/or neuron. The present invention also provides methods of screening compounds that modulate activity of an ActRII protein and/or an ActRII ligand. The compositions and methods provided herein are useful in treating diseases associated with abnormal activity of an ActRII protein and/or an ActRII ligand.
Claims35
A pharmaceutical preparation for treating an ActRII-associated disorder, comprising:
- a) a soluble ActRII polypeptide;
- and
- b) a pharmaceutically acceptable carrier.
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10-12. (canceled)
14-15. (canceled)
A stabilized ActRII polypeptide comprising:
- a soluble ActRII polypeptide and a second portion comprising a stabilizing domain.
An isolated polynucleotide comprising a coding sequence for a soluble ActRII polypeptide selected from the group consisting of:
- a) a polypeptide comprising an amino acid sequence selected from SEQ ID NOs:
- 1-2 and 9-12;
- b) a polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from SEQ ID NOs:
- 1-2 and 9-12;
- and
- c) a polypeptide comprising at least 10 consecutive amino acids selected from SEQ ID NOs:
- 1-2 and 9-12,
- wherein said soluble ActRII polypeptide has one or more of the following characteristics:
- i) binds to an ActRII ligand with a Kd of at least 10−5 M;
- and
- ii) inhibits ActRII signaling in a cell.
An isolated polynucleotide, comprising:
- a) a sequence encoding an ActRII polypeptide;
- b) a stop codon;
- and
- c) a sequence that is at least 90% identical to a sequence encoding an ActRII polypeptide;
- wherein the stop codon is positioned between the sequence of (a) and the sequence of (c) or within the sequence of (c).
An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NOs:
- 7 and 8, said isolated polynucleotide further comprising a non-natural transcription termination codon at least six hundred nucleotides before the 3′-terminus.
25-29. (canceled)
A method for treating a subject having a disorder associated with muscle loss or insufficient muscle growth, comprising administering to the subject an effective amount of a soluble ActRII polypeptide.
34-37. (canceled)
A method for treating a subject having a disorder associated with neurodegeneration, comprising administering to the subject an effective amount of a soluble ActRII polypeptide.
39-40. (canceled)
A method for treating a subject having a disorder associated with abnormal cell growth and differentiation, comprising administering to the subject an effective amount of a soluble ActRII polypeptide.
42-43. (canceled)
A method for increasing growth of a tissue or decreasing loss of a tissue in a subject, comprising administering to the subject an effective amount of a soluble ActRII polypeptide sufficient to increase growth of the tissue or decrease loss of the tissue, wherein the tissue is selected from the group consisting of:
- bone, cartilage, muscle, fat, and neuron.
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A method for decreasing the body fat content or reducing the rate of increase in body fat content in a subject, comprising administering to a subject in need thereof an effective amount of a soluble ActRII polypeptide.
47-88. (canceled)
Dependencies are inferred from the claim text.