Methods of using humanized antibodies and compositions for binding sphingosine-1-phosphate
AssigneeLpath, Inc.
InventorsRoger A. Sabbadini, William A. Garland, Genevieve Hansen, Steven Tarran Jones, David Williams
Life of this patent
Estimating the term…
Abstract
The present invention relates to anti-S1P agents, particularly humanized monoclonal antibodies (and antigen binding fragments thereof) specifically reactive with S1P, compositions containing such antibodies (or fragments), and the use of such antibodies (or fragments), for example, to treat diseases and conditions associated with aberrant levels of S1P.
Claims18
A method of treating a disease or disorder correlated with an aberrant level of S1P, comprising administering to a subject known or suspected to be suffering from a disease or disorder correlated with an aberrant level of sphingosine-1-phosphate (S1P) a therapeutically effective amount of an isolated humanized antibody, or an antigen binding fragment thereof, that binds S1P to effect treatment of the disease or disorder, wherein the antibody or an antigen binding fragment thereof comprises at least one heavy chain variable domain and at least one light chain variable domain, wherein:
- A. each heavy chain variable domain comprises the following:
- (i) a first sequence of amino acid residues of sequence DHTIH (SEQ ID NO:
- 13);
- (ii) a second sequence of amino acid residues selected from the group consisting of AISPRHDITKYNEMFRG (SEQ ID NO:
- 31) and CISPRHDITKYNEMFRG (SEQ ID NO:14), provided that if the second sequence of amino acid residues is CISPRHDITKYNEMFRG (SEQ ID NO:14), the heavy chain variable domain is humanized;
- and
- (iii) a third sequence of amino acid residues of sequence GGFYGSTIWFDF (SEQ ID NO:
- 15);
- and
- B. each light chain variable domain comprises the following:
- (i) a first sequence of amino acid residues of sequence ITTTDIDDDMN (SEQ ID NO:
- 10);
- (ii) a second sequence of amino acid residues of sequence EGNILRP (SEQ ID NO:
- 11);
- and
- (iii) a third sequence of amino acid residues of sequence LQSDNLPFT (SEQ ID NO:
- 12).
A method of treating a disease or disorder correlated with an aberrant level of S1P, comprising administering to a subject known or suspected to be suffering from a disease or disorder correlated with an aberrant level of S1P a therapeutically effective amount of an isolated humanized antibody, or an antigen binding fragment thereof, specifically reactive with S1P to effect treatment of the disease or disorder, wherein the antibody or an antigen binding fragment thereof comprises at least one heavy chain variable domain and at least one light chain variable domain, wherein:
- A. each heavy chain variable domain comprises:
- (i) a sequence of amino acid residues having an amino acid sequence EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMRQMPGQGLE WMGAISPRHDITKYNEMFRGQVTISADKSSSTAYLQWSSLKASDT AMYFCARGGFYGSTIWFDFWGQGTMVTVSS (SEQ ID NO:
- 32, residues 20-140, inclusive);
- or
- (ii) a sequence of amino acid residues having at least about 80% sequence identity to the amino acid sequence of A(i), above provided such sequence of amino acid residues comprises a first sequence of amino acid residues of sequence DHTIH (SEQ ID NO:
- 13), a second sequence of amino acid residues selected from the group consisting of AISPRHDITKYNEMFRG (SEQ ID NO:
- 31) and CISPRHDITKYNEMFRG (SEQ ID NO:14), and a third sequence of amino acid residues of sequence GGFYGSTIWFDF (SEQ ID NO:
- 15);
- and
- B. each light chain variable domain comprises:
- (i) a sequence of amino acid residues having an amino acid sequence ETTVTQSPSFLSASVGDRVTITCITTTDIDDDMNWFQQEPG KAPKLLISEGNILRPGVPSRFSSSGYGTDFTLTISKLQPEDF ATYYCLQSDNLPFTFGQGTKLEIK (SEQ ID NO:
- 33, residues 21-127, inclusive);
- or
- (ii) a sequence of amino acid residues having at least about 80% sequence identity to the amino acid sequence of B(i), above provided such sequence of amino acid residues comprises a first sequence of amino acid residues of sequence ITTTDIDDDMN (SEQ ID NO:
- 10), a second sequence of amino acid residues of sequence EGNILRP (SEQ ID NO:
- 11), and a third sequence of amino acid residues of sequence LQSDNLPFT (SEQ ID NO:
- 12).
Dependencies are inferred from the claim text.