US2017342146A1PendingUtilityA1
Nanobodies against tumor necrosis factor-alpha
Est. expiryMay 18, 2025(expired)· nominal 20-yr term from priority
Inventors:Els Anna Alice Beirnaert
A61P 37/06A61P 7/06A61P 43/00A61P 37/08A61P 9/10A61P 5/40A61P 37/04A61P 5/14A61P 7/00A61P 37/02A61P 37/00A61P 9/00A61P 3/02A61P 25/08A61P 29/00A61P 25/18A61P 25/00A61P 25/16A61P 29/02A61P 27/02A61P 35/00A61P 31/18A61P 25/28A61P 3/10A61P 25/32A61P 25/24A61P 31/08A61P 25/36A61P 27/16A61P 15/08A61P 17/02A61P 17/06A61P 15/00A61P 11/06A61P 11/00A61P 1/04A61P 17/00A61P 13/12A61P 19/02A61P 21/04A61P 1/16C07K 2317/31C07K 2319/31C07K 2317/565C07K 2317/22C07K 16/468C07K 2317/24C12N 5/10A61K 2039/505A61K 39/395C07K 16/18C07K 16/241C07K 14/525C12N 15/09C12P 21/02C07K 16/24B82Y 5/00C07K 19/00
62
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.
Claims
exact text as granted — not AI-modified1 .- 111 . (canceled)
112 . A method for treating a Tumor Necrosis Factor-α (TNF-α) related disorder comprising administering, to a subject in need thereof, an effective amount of a polypeptide comprising an immunoglobulin variable domain that binds an epitope of TNF-α:
(a) that comprises the following amino acid residues of TNF-α: Gln at position 88, Lys at position 90, and/or Glu at position 146; or
(b) that is the same TNF-α epitope as that bound by a polypeptide comprising any of the following sets of CDR sequences:
(SEQ ID NO: 15)
CDR1 is DYWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 34)
CDR3 is SPSGFN;
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF;
or
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 25)
CDR2 is EINTNGLITKYVDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF.
113 . The method according to claim 112 , wherein the polypeptide is able to pass through the gastric environment without being inactivated.
114 . The method according to claim 112 , wherein the polypeptide inhibits TNFα/TNFα-receptor interactions.
115 . The method according to claim 112 , wherein the immunoglobulin variable domain competes for the binding to, or displaces the binding to, the epitope of TNF-α by a polypeptide comprising the following sets of CDR sequences:
(SEQ ID NO: 15)
CDR1 is DYWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 34)
CDR3 is SPSGFN;
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF;
or
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 25)
CDR2 is EINTNGLITKYVDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF.
116 . The method according to claim 115 , wherein the immunoglobulin variable domain competes for the binding to, or displaces the binding to, the epitope of TNF-α by a polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 52, 53, 54, 76, 77, 95, or 96.
117 . The method according to claim 116 , wherein the immunoglobulin variable domain competes for the binding to, or displaces the binding to, the epitope of TNF-α by a polypeptide comprising the amino acid sequence of SEQ ID NO: 96.
118 . The method according to claim 112 , wherein the immunoglobulin variable domain is a single domain antibody, a heavy chain variable domain, or a VHH.
119 . The method according to claim 112 , wherein the polypeptide is administered as a pharmaceutical composition.
120 . The method according to claim 112 , wherein the polypeptide is administered orally.
121 . The method according to claim 120 , wherein the polypeptide is administered as a pharmaceutical composition.
122 . The method according to claim 121 , wherein the pharmaceutical composition comprises an enteric coating that resists the gastric environment and passes into the intestines.
123 . The method according to claim 120 , wherein the pharmaceutical composition is an ingestible tablet, buccal tablet, troche, capsule, elixir, suspension, syrup, or wafer.
124 . The method according to claim 112 , wherein the disorder is Crohn's disease, ulcerative colitis or inflammatory bowel syndrome.
125 . The method according to claim 119 , wherein the pharmaceutical composition is a suppository.
126 . The method according to claim 112 , wherein the polypeptide comprises at least two immunoglobulin variable domains that bind an epitope of TNF-α.
127 . The method according to claim 112 , wherein the polypeptide consists of a single domain antibody, a heavy chain variable domain, or a VHH.
128 . The method according to claim 112 , wherein the polypeptide is humanized.
129 . A polypeptide comprising an immunoglobulin variable domain that binds an epitope of TNF-α:
(a) that comprises the following amino acid residues of TNF-α: Gln at position 88, Lys at position 90, and/or Glu at position 146; or
(b) that is the same TNF-α epitope as that bound by a polypeptide comprising any of the following sets of CDR sequences:
(SEQ ID NO: 15)
CDR1 is DYWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 34)
CDR3 is SPSGFN;
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF;
or
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 25)
CDR2 is EINTNGLITKYVDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF.
130 . The polypeptide according to claim 129 , wherein the polypeptide is able to pass through the gastric environment without being inactivated.
131 . The polypeptide according to claim 129 , wherein the polypeptide inhibits TNFα/TNFα-receptor interactions.
132 . The polypeptide according to claim 129 , wherein the immunoglobulin variable domain competes for the binding to, or displaces the binding to, the epitope of TNF-α by a polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 52, 53, 54, 76, 77, 95, or 96.
133 . The polypeptide according to claim 132 , wherein the immunoglobulin variable domain competes for the binding to, or displaces the binding to, the epitope of TNF-α by a polypeptide comprising the amino acid sequence of SEQ ID NO: 96.
134 . The polypeptide according to claim 129 , wherein the immunoglobulin variable domain displaces the binding to the epitope of TNF-α by a polypeptide comprising the following sets of CDR sequences:
(SEQ ID NO: 15)
CDR1 is DYWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
and
(SEQ ID NO: 34)
CDR3 is SPSGFN;
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 22)
CDR2 is EINTNGLITKYPDSVKG;
(SEQ ID NO: 35)
and CDR3 is SPSGSF;
or
(SEQ ID NO: 18)
CDR1 is VSWMY;
(SEQ ID NO: 25)
CDR2 is EINTNGLITKYVDSVKG;
and
(SEQ ID NO: 35)
CDR3 is SPSGSF.
135 . The polypeptide according to claim 129 , wherein the immunoglobulin variable domain is a single domain antibody, a heavy chain variable domain, or a VHH.
136 . The polypeptide according to claim 129 , wherein the polypeptide comprises at least two immunoglobulin variable domains that bind an epitope of TNF-α.
137 . The polypeptide according to claim 129 , wherein the polypeptide consists of a single domain antibody, a heavy chain variable domain, or a VHH.
138 . The polypeptide according to claim 129 , wherein the polypeptide is humanized.
139 . A pharmaceutical composition comprising a polypeptide according to claim 129 .
140 . The pharmaceutical composition according to claim 139 , further comprising one or more excipients.
141 . The pharmaceutical composition according to claim 139 , wherein the composition is an ingestible tablet, buccal tablet, troche, capsule, elixir, suspension, syrup, or wafer.
142 . The pharmaceutical composition according to claim 139 , wherein the composition comprises an enteric coating that resists the gastric environment.
143 . The pharmaceutical composition according to claim 139 , wherein the composition is a suppository.Join the waitlist — get patent alerts
Track US2017342146A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.