Anti-TREM1 antibodies and related methods
Inventors
Chan, Christopher • Pal, Aritra • Sriram, Venkataraman • Presta, Leonard G. • LE, Tiep Tu • Liang, Linda
Assignees
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Publication Number
US-12065491-B2
Publication Date
2024-08-20
Expiration Date
Abstract
Provided herein are anti-TREM1 antibodies and related methods of making and using anti-TREM1 antibodies. Also provided are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM1 antibody or antigen binding fragment thereof.
Core Innovation
The invention relates to increasing an immune response in a subject by administering an isolated antibody that binds to TREM1. The antibody comprises a variable heavy chain and a variable light chain with specified three heavy chain CDR sequences and three light chain CDR sequences, including CDR-H1, CDR-H2, CDR-L1, CDR-L2, and CDR-L3 defined by SEQ ID NOs: 23, 24, 26, 27, and 28.
CDR-H3 is defined as the sequence set forth in SEQ ID NO: 29, wherein X is glutamine (Q), leucine (L), isoleucine (I), or glutamic acid (E). The disclosure also describes functional characterization of anti-TREM1 antibodies and defines antibody properties that bind human TREM1, including competitive binding criteria, epitope targeting, and binding potency by Biacore.
A related aspect is treating cancer in a subject by administering the same type of isolated TREM1-binding antibody with the specified variable heavy chain and variable light chain CDR configurations. The document additionally describes targeting specificity for non-stimulatory myeloid cells in cancer contexts, reduced off-tumor or stimulatory cell binding, and immune effector mechanisms including ADCC, CDC, ADCP, Fcγ receptor engagement, and induction of cytokines and chemokines.
Claims Coverage
The independent claim set covers 2 inventive features: increasing an immune response by administering a defined isolated TREM1-binding antibody, and treating cancer by administering the same defined isolated TREM1-binding antibody. The claim framework is centered on the antibody sequence specification, with the independent-claim divergence being the clinical purpose.
TREM1-binding antibody with specified VH and VL CDR sequences
An isolated antibody that binds to TREM1 comprising a variable heavy chain with three heavy chain CDR sequences and a variable light chain with three light chain CDR sequences, wherein CDR-H1 comprises SEQ ID NO: 23, CDR-H2 comprises SEQ ID NO: 24, CDR-H3 comprises SEQ ID NO: 29 wherein X is glutamine (Q), leucine (L), isoleucine (I), or glutamic acid (E), CDR-L1 comprises SEQ ID NO: 26, CDR-L2 comprises SEQ ID NO: 27, and CDR-L3 comprises SEQ ID NO: 28.
Increasing an immune response by administering the specified TREM1-binding antibody
A method of increasing an immune response in a subject comprising administering to the subject the isolated TREM1-binding antibody defined by the specified VH and VL CDR sequence composition.
Treating cancer by administering the specified TREM1-binding antibody
A method of treating cancer in a subject comprising administering to the subject the isolated TREM1-binding antibody defined by the specified VH and VL CDR sequence composition.
Overall, the claim coverage centers on administering an isolated TREM1-binding antibody defined by specific VH and VL CDR sequences, including CDR-H3 with X limited to Q, L, I, or E. Independent claims apply this antibody framework to increasing an immune response and treating cancer.
Stated Advantages
Afucosylated TREM1-binding antibodies PI-64052 (M100L) and PI-64062 (M100Q) enhance FcγR binding relative to fucosylated counterparts and exhibit improved EC50 in TREM1-overexpressing cellular contexts.
The antibodies are described as showing reduced off-tumor or stimulatory cell binding in contrast to stimulatory myeloid cells.
The disclosure links immune complex formation and Fcγ receptor engagement, including CD16, with downstream effects including induction of cytokines and chemokines and upregulation of co-stimulatory molecules such as CD40, HLA-DR, CD80, and CD86.
Documented Applications
Increasing an immune response in a subject.
Treating cancer in a subject.
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