Compositions and methods for binding sphingosine-1-phosphate
View Patent ↗The present invention relates to anti-S1P agents, for example, humanized monoclonal antibodies, and their uses for detection of S1P or for treatment of diseases and conditions associated with S1P.
1. An isolated humanized antibody, or an antigen binding fragment thereof, that binds sphingosine-1-phosphate and comprises at least one heavy chain and at least one light chain, wherein:
A. each heavy chain comprises a heavy chain variable domain comprising a sequence of amino acid residues having an amino acid sequence
[SEQ ID NO: 27]
EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMR
QMPGQGLEWMGAISPRHDITKYNEMFRGQVTISADK
SSSTAYLQWSSLKASDTAMYFCARGGFYGSTIWFDF
WGQGTMVTVSS;
or
and
B. each light chain comprises a light chain variable domain comprising a sequence of amino acid residues having an amino acid sequence
[SEQ ID NO: 29]
ETTVTQSPSFLSASVGDRVTITCITTTDIDDDMNWFQQEPG
KAPKLLISEGNILRPGVPSRFSSSGYGTDFTLTISKLQPEDF
ATYYCLQSDNLPFTFGQGTKLEIK.
2. An isolated humanized antibody according to claim 1 , wherein:
A. each heavy chain comprises a sequence of amino acid residues having an amino acid sequence
[SEQ ID NO: 35]
EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMRQMPGQGLE
WMGAISPRHDITKYNEMFRGQVTISADKSSSTAYLQWSSLKASDTA
MYFCARGGFYGSTIWFDFWGQGTMVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTC
PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG;
and
B. each light chain comprises a sequence of amino acid residues having an amino acid sequence
[SEQ ID NO:32]
ETTVTQSPSFLSASVGDRVTITCITTTDIDDDMNWFQQEPGKAPKL
LISEGNILRPGVPSRFSSSGYGTDFTLTISKLQPEDFATYYCLQSD
NLPFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
DYEKHKVYACEVTHQGLSSPVTKSFNRGEC.
3. An isolated humanized antibody according to claim 2 , wherein each heavy chain comprises a sequence of amino acid residues having an amino acid sequence
[SEQ ID NO: 31]
EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMRQMPGQGLEW
MGAISPRHDITKYNEMFRGQVTISADKSSSTAYLQWSSLKASDTAMY
FCARGGFYGSTIWFDFWGQGTMVTVSSASTKGPSVFPLAPSSKSTSG
GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS
VVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPA
PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN
KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK.
4. An isolated antibody, or an antigen binding fragment thereof, that binds sphingosine-1-phosphate, wherein:
A. each heavy chain comprises the same heavy chain variable domain amino acid sequence as the heavy chain variable domain encoded by the heavy chain gene in vector pATH1009 in ATCC Accession No. PTA-8421; and
B. each light chain comprises the same light chain variable domain amino acid sequence as the light chain variable domain encoded by the light chain gene in vector pATH1009 in ATCC Accession No. PTA-8421.
5. An isolated humanized antibody, or an antigen binding fragment thereof, according to claim 1 wherein at least one amino acid residue of the antibody is glycosylated.
6. A pharmaceutical composition comprising an isolated humanized antibody, or an antigen binding fragment thereof, according to claim 1 and a pharmaceutically acceptable carrier.
7. An isolated antibody, or an antigen binding fragment thereof, that binds sphingosine-1-phosphate, wherein:
A. each heavy chain comprises the same heavy chain as the heavy chain of the antibody expressed by CHO cell line LH1 275, as deposited under accession number ATCC PTA-8422; and
B. each light chain comprises the same light chain as the light chain of the antibody expressed by CHO cell line LH1 275, as deposited under accession number ATCC PTA-8422.
8. An isolated antibody, or an antigen binding fragment thereof, according to claim 4 wherein at least one amino acid residue of the antibody is glycosylated.
9. A pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, according to claim 4 and a pharmaceutically acceptable carrier.
10. An isolated antibody, or an antigen binding fragment thereof, according to claim 7 wherein at least one amino acid residue of the antibody is glycosylated.
11. A pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, according to claim 7 and a pharmaceutically acceptable carrier.