OB polypeptides and modified forms as modulators of body weight
First Claim
1. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-167 of SEQ ID NOS:
- 2 or 4, wherein one or more amino acids selected from the group consisting of amino acids 53, 56, 71, 85, 89, 92, 95, 98, 110, 118, 121, 122, 126, 127, 128, 129, 132, 139, 157, 159, 163, and 166 is substituted with another amino acid.
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Accused Products
Abstract
The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In one of its broadest aspects, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention. The invention further relates to host cells transfected or transformed with an appropriate expression vector and to their use in the preparation of the modulators of the invention. Also provided are antibodies to the OB polypeptide. Moreover, a method for modulating body weight of a mammal is provided.
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Citations
27 Claims
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1. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-167 of SEQ ID NOS:
- 2 or 4, wherein one or more amino acids selected from the group consisting of amino acids 53, 56, 71, 85, 89, 92, 95, 98, 110, 118, 121, 122, 126, 127, 128, 129, 132, 139, 157, 159, 163, and 166 is substituted with another amino acid.
- View Dependent Claims (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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2. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-167 of SEQ ID NO:
- 4 wherein the analog is selected from the group consisting of polypeptides wherein;
(a) the serine residue at position 53 is substituted with glycine, alanine, valine, cysteine, methionine, or threonine;
(b) the serine residue at position 98 is substituted with glycine, alanine, valine, cysteine, methionine, or threonine; and
(c) the arginine residue at position number 92 is substituted with asparagine, lysine, histidine, glutamine, glutamic acid, aspartic acid, serine, threonine, methionine, or cysteine.
- 4 wherein the analog is selected from the group consisting of polypeptides wherein;
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3. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide, capable of modulating body weight, comprising amino acids 22-167 of SEQ ID NOS:
- 2 or 4 or amino acids 22-166 of SEQ ID NO;
5 or 6 wherein said polypeptide has an N-terminal amino acid sequence selected from the group consisting of;(a) SEQ ID NO;
38;
(b) SEQ ID NO;
98;
(c) SEQ ID NO;
26;
(d) SEQ ID NO;
27;
(e) SEQ ID NO;
28;
(f) SEQ ID NO;
99; and
(g) glycine-serine-proline.
- 2 or 4 or amino acids 22-166 of SEQ ID NO;
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4. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-167 of SEQ ID NOS:
- 2 or 4, wherein one or more amino acids selected from the group consisting of amino acids 53, 56, 71, 85, 89, 92, 95, 98, 110, 118, 121, 122, 126, 127, 128, 129, 132, 139, 157, 159, 163, and 166 is substituted with another amino acid and wherein said analog has an N-terminal amino acid sequence selected from the group consisting of;
(a) SEQ ID NO;
38;
(b) SEQ ID NO;
98;
(c) SEQ ID NO;
26;
(d) SEQ ID NO;
27;
(e) SEQ ID NO;
28;
(f) SEQ ID NO;
99; and
(g) glycine-serine-proline.
- 2 or 4, wherein one or more amino acids selected from the group consisting of amino acids 53, 56, 71, 85, 89, 92, 95, 98, 110, 118, 121, 122, 126, 127, 128, 129, 132, 139, 157, 159, 163, and 166 is substituted with another amino acid and wherein said analog has an N-terminal amino acid sequence selected from the group consisting of;
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5. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-166 of SEQ ID NOS:
- 5 or 6, wherein one or more amino acids selected from the group consisting of amino acids 52, 55, 70, 84, 88, 91, 94, 97, 109, 117, 120, 121, 125, 126, 127, 128, 131, 138, 156, 158, 162, and 165 is substituted with another amino acid.
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6. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-166 of SEQ ID NO:
- 6 wherein the analog is selected from the group consisting of polypeptides wherein;
(a) the serine residue at position 52 is substituted with glycine, alanine, valine, cysteine, methionine, or threonine;
(b) the serine residue at position 97 is substituted with glycine, alanine, valine, cysteine, methionine, or threonine; and
(c) the arginine residue at position number 91 is substituted with asparagine, lysine, histidine, glutamine, glutamic acid, aspartic acid, serine, threonine, methionine, or cysteine.
- 6 wherein the analog is selected from the group consisting of polypeptides wherein;
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7. A method for modifying body weight of an animal, the method comprising administering to the animal an effective amount of an OB polypeptide analog, capable of modulating body weight, comprising amino acids 22-166 of SEQ ID NOS:
- 5 or 6, wherein one or more amino acids selected from the group consisting of amino acids 52, 55, 70, 84, 88, 91, 94, 97, 109, 117, 120, 121, 125, 126, 127, 128, 131, 138, 156, 158, 162, and 165 is substituted with another amino acid and wherein said analog has an N-terminal amino acid sequence selected from the group consisting of;
(a) SEQ ID NO;
38;
(b) SEQ ID NO;
98;
(c) SEQ ID NO;
26;
(d) SEQ ID NO;
27;
(e) SEQ ID NO;
28;
(f) SEQ ID NO;
99; and
(g) glycine-serine-proline.
- 5 or 6, wherein one or more amino acids selected from the group consisting of amino acids 52, 55, 70, 84, 88, 91, 94, 97, 109, 117, 120, 121, 125, 126, 127, 128, 131, 138, 156, 158, 162, and 165 is substituted with another amino acid and wherein said analog has an N-terminal amino acid sequence selected from the group consisting of;
Specification