Treatment of coronary disorders using TNFalpha inhibitors
First Claim
Patent Images
1. A method of treating or preventing a coronary disorder in a subject comprising administering a therapeutically effective amount of a TNFα
- antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
with a Kd of 1×
10−
8 M or less and a Koff rate constant of 1×
10−
3 s−
1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα
cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×
10−
7 M or less, such that the coronary disorder is treated or prevented.
1 Assignment
0 Petitions
Accused Products
Abstract
Methods for treating coronary disease in which TNFα activity is detrimental are described.
-
Citations
26 Claims
-
1. A method of treating or preventing a coronary disorder in a subject comprising administering a therapeutically effective amount of a TNFα
- antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
with a Kd of 1×
10−
8 M or less and a Koff rate constant of 1×
10−
3 s−
1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα
cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×
10−
7 M or less, such that the coronary disorder is treated or prevented. - View Dependent Claims (4, 5, 6)
- antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
-
2. A method of treating or preventing a coronary disorder in a subject comprising administering a therapeutically effective amount a TNFα
- antibody, or an antigen-binding fragment thereof, with the following characteristics;
a) dissociates from human TNFα
with a Koff rate constant of 1×
10−
3 s−
1 or less, as determined by surface plasmon resonance;
b) has a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO;
3, or modified from SEQ ID NO;
3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9;
c) has a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO;
4, or modified from SEQ ID NO;
4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12, such that said coronary disorder is treated or prevented.
- antibody, or an antigen-binding fragment thereof, with the following characteristics;
-
3. A method of treating or preventing a coronary disorder in a subject comprising administering a therapeutically effective amount a TNFα
- antibody, or an antigen-binding fragment thereof, with a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO;
2, such that said coronary disorder is treated or prevented.
- antibody, or an antigen-binding fragment thereof, with a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO;
-
7. A method of treating or preventing restenosis in a subject comprising administering a therapeutically effective amount of a TNFα
- antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
with a Kd of 1×
10−
8 M or less and a Koff rate constant of 1×
10−
3 s−
1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα
cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×
10−
7 M or less, such that said restenosis is treated or prevented. - View Dependent Claims (10, 11)
- antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
-
8. A method of treating or preventing restenosis in a subject comprising administering a therapeutically effective amount a TNFα
- antibody, or an antigen-binding fragment thereof, with the following characteristics;
a) dissociates from human TNFα
with a Koff rate constant of 1×
10−
3 s−
1 or less, as determined by surface plasmon resonance;
b) has a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO;
3, or modified from SEQ ID NO;
3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9;
c) has a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO;
4, or modified from SEQ ID NO;
4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12, such that said restenosis is treated or prevented.
- antibody, or an antigen-binding fragment thereof, with the following characteristics;
-
9. A method of treating or preventing restenosis in a subject comprising administering a therapeutically effective amount a TNFα
- antibody, or an antigen-binding fragment thereof, with a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO;
2, such that said restenosis is treated or prevented.
- antibody, or an antigen-binding fragment thereof, with a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO;
-
12. A method for inhibiting human TNFα
- activity in a human subject suffering from a coronary disorder comprising administering a therapeutically effective amount of a TNFα
antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
with a Kd of 1×
10−
8 M or less and a Koff rate constant of 1×
10−
3 s−
1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα
cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×
10−
7 M or less. - View Dependent Claims (13, 14, 15)
- activity in a human subject suffering from a coronary disorder comprising administering a therapeutically effective amount of a TNFα
-
16. A method for inhibiting human TNFα
- activity in a human subject suffering from restenosis, comprising administering a therapeutically effective amount of a TNFα
antibody, or an antigen-binding fragment thereof, to the subject, wherein the antibody dissociates from human TNFα
with a Kd of 1×
10−
8 M or less and a Koff rate constant of 1×
10−
3 s−
1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα
cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×
10−
7 M or less. - View Dependent Claims (17)
- activity in a human subject suffering from restenosis, comprising administering a therapeutically effective amount of a TNFα
- 18. A method of treating or preventing a coronary disorder in a subject comprising administering a therapeutically effective amount of D2E7, or an antigen-binding fragment thereof, to the subject, such that the coronary disorder is treated or prevented.
-
21. A method of treating a subject suffering from restenosis comprising administering a therapeutically effective amount of D2E7, or an antigen-binding fragment thereof, to the subject, such that said restenosis is treated.
- 23. A method of treating a subject suffering from or at risk of developing restenosis comprising administering a therapeutically effective amount of D2E7, or an antigen-binding fragment thereof, and at least one additional therapeutic agent to the subject, such that the coronary disorder is treated.
-
25. A kit comprising:
-
a) a pharmaceutical composition comprising a TNFα
antibody, or an antigen binding portion thereof, and a pharmaceutically acceptable carrier; and
b) instructions for administering to a subject the TNFα
antibody pharmaceutical composition for treating a subject who is suffering from a coronary disorder.
-
Specification