Pharmaceutical compositions for binding sphingosine-1-phosphate
View Patent ↗The present invention relates to compositions that comprise an anti-S1P monoclonal antibody, antibody fragment, or derivative in a carrier, particularly a buffered, hypertonic aqueous solution, as well as to kits containing such compositions, and methods for using such compositions for treatment of diseases and conditions associated with S1P.
1. A composition comprising a pharmaceutically acceptable carrier and an antibody or an antigen-binding antibody fragment that binds sphingosine-1-phosphate (S1P) under physiological conditions, wherein the composition is hypertonic and the antibody or an antigen-binding antibody fragment 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 first sequence of amino acid residues of sequence DHTIH (SEQ ID NO: 4);
(ii) a second sequence of amino acid residues selected from the group consisting of AISPRHDITKYNEMFRG (SEQ ID NO: 6); and
(iii) a third sequence of amino acid residues of sequence GGFYGSTIWFDF (SEQ ID NO: 5); and
B. each light chain variable domain comprises the following:
(i) a first sequence of amino acid residues of sequence ITTTDIDDDMN (SEQ ID NO: 1);
(ii) a second sequence of amino acid residues of sequence EGNILRP (SEQ ID NO: 2); and
(iii) a third sequence of amino acid residues of sequence LQSDNLPFT (SEQ ID NO: 3),
wherein the composition comprises a buffered hypertonic solution having a pH between about pH 5.5 and about pH 6.5 and comprising sodium chloride in a concentration of at least about 250mM.
2. A composition according to claim 1 wherein the monoclonal antibody or an antigen-binding antibody fragment is present at a concentration of less than about 100 mg/mL, and wherein the buffered solution comprises a phosphate buffer, a citrate buffer, a histidine buffer, or a succinate buffer.
3. A composition according to claim 2 wherein the buffered hypertonic solution has a pH between about pH 5.5 to about pH 6.1.
4. A composition according to claim 1 that comprises a sodium chloride concentration selected from the group consisting of less than about 1M and less than about 500 mM.
5. A composition according to claim 4 wherein the sodium chloride concentration is selected from the group consisting less than about 300mM and less than about 450 mM.
6. A composition according to claim 2 wherein the buffered hypertonic solution further comprises a physiologically compatible non-ionic surfactant.
7. A composition according to claim 6 wherein the non-ionic surfactant is polysorbate-80 or polysorbate-20.
8. An aqueous composition, comprising:
a. a pharmaceutically acceptable carrier that comprises a buffered hypertonic solution comprising from about 250 mM to about 3M sodium chloride and having a pH that is between about pH 5.5 and about pH 6.5; and
b. an antibody or an antigen-binding antibody fragment that binds sphingosine-1-phosphate (S1P ) under physiological conditions, wherein the antibody or an antigen-binding antibody fragment is present at a concentration of less than about 100 mg/mL and 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 first sequence of amino acid residues of sequence DHTIH (SEQ ID NO: 4);
(ii) a second sequence of amino acid residues selected from the group consisting of AISPRHDITKYNEMFRG (SEQ ID NO: 6); and
(iii) a third sequence of amino acid residues of sequence GGFYGSTIWFDF (SEQ ID NO: 5); and
B. each light chain variable domain comprises the following:
(i) a first sequence of amino acid residues of sequence ITTTDIDDDMN (SEQ ID NO: 1);
(ii) a second sequence of amino acid residues of sequence EGNILRP (SEQ ID NO: 2); and
(iii) a third sequence of amino acid residues of sequence LQSDNLPFT (SEQ ID NO: 3).
9. An aqueous composition according to claim 8 , comprising:
a. a pharmaceutically acceptable carrier that comprises a buffered hypertonic solution having a pH between about pH 5.5 and about pH 6.1;
b. the antibody or an antigen-binding antibody fragment is present at a concentration from between about 10 mg/mL to about 50 mg/mL;
c. sodium chloride in a concentration of from about 250 mM to about 1M; and
d. a physiologically compatible non-ionic surfactant selected from the group consisting of polysorbate-80 and polysorbate-20.
10. An aqueous composition according to claim 9 , comprising:
a. a pharmaceutically acceptable carrier wherein the buffered hypertonic solution is selected from the group consisting of a phosphate-buffered solution, a citrate-buffered solution, a histidine-buffered solution, and a succinate-buffered solution;
b. the antibody or an antigen-binding antibody fragment is present at a concentration selected from the group consisting of about 11 mg/mL and about 42 mg/mL;
c. sodium chloride in a concentration selected from the group consisting of about 250 mM, about 300 mM, about 450 mM, about 550 mM, about 750 mM, and about 1M; and
d. about 200 ppm or less of polysorbate-80 or polysorbate-20.
11. An article of manufacture comprising a composition according to claim 1 in an aseptically sealed container.
12. A kit comprising an article according to claim 11 and instructions for use of the aqueous composition.