Compositions and methods of use for an ephrin receptor

A purified antibody that binds immunospecifically to a polypeptide selected from the group consisting of:

• a) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• b) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• c) the polypeptide of (a) and (b), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation modulatory activity;
• d) a fragment of the polypeptide of (a), (b), or (c), which fragment retains cellular proliferation modulatory activity;
• and
• e) a fragment of the polypeptide of (a), (b), or (c), which fragment retains kinase activity.

An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

• a) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• b) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• c) the polypeptide of (a) and (b), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation modulatory activity;
• d) a fragment of the polypeptide of (a), (b), or (c), which fragment retains cellular proliferation modulatory activity;
• and
• e) a fragment of the polypeptide of (a), (b), or (c), which fragment retains kinase activity.

An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of:

• (a) a mature form of an amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• (b) a variant of a mature form of an amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of the amino acid residues from the amino acid sequence of said mature form;
• (c) an amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• (d) a variant of an amino acid sequence selected from the group consisting SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of amino acid residues from said amino acid sequence;
• (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising an amino acid sequence chosen from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36, or a variant of said polypeptide, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of amino acid residues from said amino acid sequence;
• and
• (f) a nucleic acid molecule comprising the complement of (a), (b), (c), (d) or (e).

A method of preparing a pharmaceutical composition comprising combining at least one antibody effective in treating, preventing, or delaying a cell proliferation-associated disorder with a pharmaceutically acceptable carrier, wherein said antibody binds immunospecifically to a polypeptide selected from the group consisting of:

• a) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• b) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• c) the polypeptide of (a) and (b), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation modulatory activity;
• d) a fragment of the polypeptide of (a), (b), or (c), which fragment retains cellular proliferation modulatory activity;
• and
• e) a fragment of the polypeptide of (a), (b), or (c), which fragment retains kinase activity.

A method for determining the presence of or predisposition to a cell proliferation-associated disorder associated with altered levels of a polypeptide selected from the group consisting of:

• a) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• b) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• c) the polypeptide of (a) and (b), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation modulatory activity;
• d) a fragment of the polypeptide of (a), (b), or (c), which fragment retains cellular proliferation modulatory activity;
• and
• e) a fragment of the polypeptide of (a), (b), or (c), which fragment retains kinase activity
• in a first mammalian subject, the method comprising:
• i) measuring the amount of the polypeptide in a sample from the first mammalian subject using an antibody that immunospecifically binds to the polypeptide;
• and
• ii) comparing the amount of the polypeptide in the sample of step (i) to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disorder;
• wherein an alteration in the level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disorder.

A drug formulation for treating, preventing, or delaying a cell proliferation-associated disorder in a subject comprising:

• a) a therapeutically effective amount of an antibody that immunospecifically binds a polypeptide selected from the group consisting of:
• i) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• ii) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• iii) the polypeptide of (i) and (ii), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation activity;
• iv) a fragment of the polypeptide of (i), (ii), or (iii), which fragment retains cellular proliferation activity;
• and
• v) a fragment of the polypeptide of (a), (b), or (c), which fragment retains kinase activity, and
• b) a formulation buffer.

A method of modulating the proliferation of a mammalian cell comprising contacting the cell with an antibody that immunospecifically binds to a polypeptide selected from the group consisting of:

• i) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28,30, 32, 34, and 36;
• ii) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• iii) the polypeptide of (i) and (ii), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation activity;
• iv) a fragment of the polypeptide of (i), (ii), or (iii), which fragment retains cellular proliferation modulatory activity.

A method of modulating blood vessel formation in a mammal, comprising contacting the mammal with an antibody that immunospecifically binds to a polypeptide selected from the group consisting of:

• i) a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36;
• ii) a mature form of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32,34, and 36;
• iii) the polypeptide of (i) and (ii), wherein one or more amino acid substitutions are made to the polypeptide to produce a variant, provided that the variant is no more than 15% divergent in sequence from the polypeptide, and provided that said variant retains cellular proliferation activity;
• iv) a fragment of the polypeptide of (i), (ii), or (iii), which fragment retains cellular proliferation modulatory activity;
• v) a fragment of the polypeptide of (i), (ii), or (iii), which fragment retains kinase activity.