IL-17A binding proteins
Inventors
Edwards, Bryan • LASHMAR, Ulla • MCGUINNESS, Brian • ROMANOS, Mike • Sandal, Thomas • TENG, Yumin
Assignees
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Publication Number
US-11667705-B2
Publication Date
2023-06-06
Expiration Date
Abstract
Binding molecules to IL-17A. The binding molecules are useful in the treatment of disorders, for example psoriasis.
Core Innovation
The invention concerns a binding molecule comprising a single domain antibody that binds human IL-17A. The single domain antibody includes a human heavy chain variable immunoglobulin domain (V_H) containing a CDR1, a CDR2, and a CDR3, with specific amino-acid sequences defined by SEQ ID NO. 5, SEQ ID NO. 6, and SEQ ID NO. 7.
The patent further characterizes IL-17A-binding human single-domain V_H antibody variants defined by CDR1, CDR2, and CDR3 amino-acid sequences using multiple family lineages and SEQ ID assignments with homology ranges. Functional potency and affinity criteria are used, including IL-17-induced IL-6 inhibition IC50 and binding KD measured by BIAcore.
The disclosed constructs include tandem V_H designs described as bivalent and/or biparatopic, and the document also includes pharmaceutical compositions that comprise a pharmaceutical carrier and the IL-17A binding single domain antibody. The documented framework supports inhibiting IL-17A activity and producing and testing these binders, using sequence-defined antibody families and described binding and functional characterization.
Claims Coverage
The independent claims cover two inventive features: an IL-17A-binding single-domain antibody defined by fixed CDR1, CDR2, and CDR3 sequences, and a pharmaceutical composition including a carrier and the same IL-17A-binding single-domain antibody.
IL-17A-binding single-domain antibody with defined CDR1/2/3 sequences
A binding molecule comprising a single domain antibody that binds human IL-17A, comprising a human heavy chain variable immunoglobulin domain (V_H) comprising a CDR1, a CDR2, and a CDR3 sequence, wherein the CDR1 sequence comprises the amino acid sequence of SEQ ID NO. 5, the CDR2 sequence comprises the amino acid sequence of SEQ ID NO. 6, and the CDR3 sequence comprises the amino acid sequence of SEQ ID NO. 7.
Pharmaceutical composition with IL-17A-binding V_H defined by CDR1/2/3
A pharmaceutical composition comprising a pharmaceutical carrier and a binding molecule that binds human IL-17A, wherein the binding molecule comprises a human heavy chain variable immunoglobulin domain (V_H) comprising a CDR1, a CDR2, and a CDR3 sequence, wherein the CDR1 sequence comprises the amino acid sequence of SEQ ID NO. 5, the CDR2 sequence comprises the amino acid sequence of SEQ ID NO. 6, and the CDR3 sequence comprises the amino acid sequence of SEQ ID NO. 7.
Across the independent claims, the core coverage is directed to IL-17A-binding single-domain V_H antibodies in which the V_H CDR1, CDR2, and CDR3 are fixed to specific SEQ ID NOs. The composition claim further limits the same binding molecule to a pharmaceutical composition comprising a pharmaceutical carrier.
Stated Advantages
IL-17A binding specificity is described with limited cross-reactivity to other IL-17 family members.
Functional inhibition is described for IL-17A activity, including inhibition of IL-17A-driven IL-6 production.
Affinity and potency metrics are described for the IL-17A binding antibodies, including KD and IC50 ranges.
Documented Applications
A pharmaceutical composition is described for use in treating at least one selected disease or condition by administering an effective amount of the pharmaceutical composition.
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