US 2018/0022803 A1 · ANTIBODIES TO L-TYPE VOLTAGE GATED CHANNELS AND RELATED METHODS

Abstract

Provided are antibodies, and antigen-binding fragments thereof, which specifically bind to an extracellular poor loop of an alpha 1a subunit of L-type voltage gated calcium channel, and related compositions, kits, and methods of use thereof, for instance, administration to a subject in need thereof to modify an immune response, for example, in the treatment of cancer.

Claims88

Dependent claims

An isolated antibody, or antigen-binding fragment thereof, which specifically binds to an alpha 1 subunit of an L-type voltage-gated calcium channel, wherein the antibody or antigen binding fragment thereof, (a) specifically binds to an amino acid sequence of an extracellular domain of a pore loop between transmembrane segments S5 and S6 of motif I of the alpha 1 subunit, or (b) competitively inhibits the binding of (a) to the alpha 1 subunit.

The isolated antibody, or antigen-binding fragment thereof, of any one of the preceding claims, which comprises a heavy chain variable region (VH) that comprises VHCDR1, VHCDR2 and VHCDR3 amino acid sequences;

and/or a light chain variable region (LH) that comprises VLCDR1, VLCDR2 and VLCDR3 amino acid sequences, which are selected from:
(A) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:14-16;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:18-20;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(B) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:22-24;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:26-28;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(C) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:30-32;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:34-36;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(D) (i) VHCDR1 and VHCDR2 comprise, respectively, the amino acid sequences of SEQ ID NOS:38-39;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:42-44;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(E) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:46-48;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:50-52;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(F) (i) VHCDR1 and VHCDR2 comprise, respectively, the amino acid sequences of SEQ ID NOS:54-55;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:58-60;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(G) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:62-64;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(H) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:70-72;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:74-76;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(I) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:78-80;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:82-84;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(J) (i) VHCDR1, VHCDR2 and VHCDR3 comprise, respectively, the amino acid sequences of SEQ ID NOS:86-88;
and (ii) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:90-92;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
(K) (i) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:98-100;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions;
and
(L) (i) VLCDR1, VLCDR2 and VLCDR3 comprise, respectively, the amino acid sequences of (i) SEQ ID NOS:106-108;
including variants thereof where at least one of said VHCDR or VLCDR amino acid sequences is modified by about 1, 2, or 3 amino acid substitutions, additions, or deletions.

32 more elements

Dependencies are inferred from the claim text.

Antibodies to l-type voltage gated channels and related methods

Life of this patent

Antibodies to l-type voltage gated channels and related methods

Life of this patent

Abstract

Claims88