# US 2018/0022803 A1 · Antibodies to l-type voltage gated channels and related methods

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2018/0022803 A1
- Document ID: US20180022803A1
- Status: Published application
- Kind: A1
- Application number: 15/549,912
- Filed: 2016-02-16
- Published: 2018-01-25
- Earliest claimed: 2015-02-13
- Assignees: bioMmune Technologies Inc.
- Applicants: bioMmune Technologies Inc.
- Inventors: Wilfred Arthur Jefferies; Kyung Bok Choi; Shawna Rose Stanwood; Franz Fenninger; Brett Alexander Eyford; Lonna Munro; Cheryl Gurine Pfeifer; Reinhard Gabathuler
- Web page: https://patentgrep.com/patent/US20180022803A1

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 5/40: Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/06: Antianaemics
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 16/30: from tumour cells
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the L-type voltage-gated calcium channel is from human or mouse.

### Claim 3 (depends on 1, 2)

The isolated antibody, or antigen-binding fragment thereof, of any of claim 1 or 2, wherein the binding of the antibody or antigen binding fragment thereof to the alpha 1 subunit alters activity of the L-type voltage-gated calcium channel.

### Claim 4 (depends on 1, 2, 3)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-3, wherein the L-type voltage-gated calcium channel is Cav1.4.

### Claim 5 (depends on 4)

The isolated antibody, or antigen-binding fragment thereof, of claim 4, wherein the amino acid sequence of the extracellular domain is GPGRPGDAPHTG [SEQ ID NO: 1], or is at least 90% identical to GPGRPGDAPHTG [SEQ ID NO: 1].

### Claim 6 (depends on 1, 2, 3)

The antibody, or antigen-binding fragment thereof, of any of claims 1-3, wherein the L-type voltage-gated calcium channel is Cav1.3.

### Claim 7 (depends on 6)

The isolated antibody, or antigen-binding fragment thereof, of claim 6, wherein the amino acid sequence of the extracellular domain is LTKETEGGNHSSGKSG [SEQ ID NO 2] or is at least 90% identical to LTKETEGGNHSSGKSG [SEQ ID NO 2].

### Claim 8 (depends on 1, 2, 3)

The antibody, or antigen-binding fragment thereof, of any of claims 1-3, wherein the L-type voltage-gated calcium channel is Cav1.2.

### Claim 9 (depends on 8)

The isolated antibody, or antigen-binding fragment thereof, of claim 8, wherein the amino acid sequence of the extracellular domain is ATKADGANALGGKGA [SEQ ID NO: 3] at least 90% identical to ATKADGANALGGKGA [SEQ ID NO: 3].

### Claim 10 (depends on 1, 2, 3, 4)

The antibody, or antigen-binding fragment thereof, of any of claims 1-4, wherein the L-type voltage-gated calcium channel is Cav1.1.

### Claim 11 (depends on 10)

The isolated antibody, or antigen-binding fragment thereof, of claim 10, wherein the amino acid sequence of the extracellular domain is PMQIELRHREWVH [SEQ ID NO 4] or is at least 90% identical to PMQIELRHREWVH [SEQ ID NO 4].

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment binds to any of Cav1.4, Cav1.3, Cav1.2, or Cav1.1.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds to any three of Cav1.4, Cav1.3, Cav1.2, or Cav1.1.

### Claim 14 (depends on 13)

The isolated antibody, or antigen-binding fragment thereof, of claim 13, wherein the antibody or antigen-binding fragment thereof binds to any of Cav1.4, Cav1.3, or Cav1.2.

### Claim 15 (depends on 13)

The isolated antibody, or antigen-binding fragment thereof, of claim 13, wherein the antibody or antigen-binding fragment thereof binds to any of Cav1.4, Cav1.3, or Cav1.1.

### Claim 16 (depends on 13)

The isolated antibody, or antigen-binding fragment thereof, of claim 13, wherein the antibody or antigen-binding fragment thereof binds to any of Cav1.4, Cav1.2, or Cav1.1.

### Claim 17 (depends on 13)

The isolated antibody, or antigen-binding fragment thereof, of claim 13, wherein the antibody or antigen-binding fragment thereof binds to any of Cav1.3, Cav1.2, or Cav1.1.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds to any two of Cav1.4, Cav1.3, Cav1.2, or Cav1.1.

### Claim 19 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.4 or Cav1.3.

### Claim 20 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.4 or Cav1.2.

### Claim 21 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.4 or Cav1.1.

### Claim 22 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.3 or Cav1.2.

### Claim 23 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.3 or Cav1.1.

### Claim 24 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, wherein the antibody or antigen-binding fragment thereof binds Cav1.2 or Cav1.1.

### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds Cav1.4 and does not significantly bind Cav1.1, Cav1.2, or Cav1.3.

### Claim 26 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds Cav1.3 and does not significantly bind Cav1.1, Cav1.2, or Cav1.4.

### Claim 27 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds Cav1.2 and does not significantly bind Cav1.1, Cav1.3, or Cav1.4.

### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The isolated antibody, or antigen-binding fragment thereof, of any of claims 1-11, wherein the antibody or antigen-binding fragment thereof binds Cav1.1 and does not significantly bind Cav1.2, Cav1.3, or Cav1.4.

### Claim 29

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.

### Claim 30

The antibody, or antigen-binding fragment thereof, of any one of the preceding claims, comprising a VH sequence that is at least 90% identical to SEQ ID NO:13, 21, 29, 37, 45, 53, 61, 69, 77, or 85.

### Claim 31

The antibody, or antigen-binding fragment thereof, of any one of the preceding claims, comprising a VL sequence that is at least 90% identical to SEQ ID NO:17, 25, 33, 41, 49, 57, 73, 81, 89, 97, or 105.

### Claim 32

The antibody, or antigen-binding fragment thereof, of any one of the preceding claims, comprising a VH sequence that is at least 90% identical to SEQ ID NO: 13, 21, 29, 37, 45, 53, 61, 69, 77, or 85, and a VL sequence that is at least 90% identical to SEQ ID NO: 17, 25, 33, 41, 49, 57, 73, 81, 89, 97, or 105.

### Claim 33

The antibody, or antigen-binding fragment thereof, of any one of the preceding claims, comprising a VH sequence and a VL sequence selected from:
(A) the VH sequence of SEQ ID NO:13 and the VL sequence of SEQ ID NO:17;
(B) the VH sequence of SEQ ID NO:21 and the VL sequence of SEQ ID NO:25;
(C) the VH sequence of SEQ ID NO:29 and the VL sequence of SEQ ID NO:33;
(D) the VH sequence of SEQ ID NO:37 and the VL sequence of SEQ ID NO:41;
(E) the VH sequence of SEQ ID NO:45 and the VL sequence of SEQ ID NO:49;
(F) the VH sequence of SEQ ID NO:53 and the VL sequence of SEQ ID NO:57;
(G) the VH sequence of SEQ ID NO:69 and the VL sequence of SEQ ID NO:73;
(H) the VH sequence of SEQ ID NO:77 and the VL sequence of SEQ ID NO:81;
(I) the VH sequence of SEQ ID NO:85 and the VL sequence of SEQ ID NO:89; and
(J) a variant VH sequence and a variant VL sequence that is at least 90% identical to any of (A)-(I).

### Claim 34

A polynucleotide encoding the antibody, or antigen-binding fragment thereof, of any one of the preceding claims.

### Claim 35 (depends on 34)

A vector encoding the polynucleotide of claim 34.

### Claim 36 (depends on 34, 35)

A cell expressing the polynucleotide of claim 34 or the vector of claim 35.

### Claim 37

A method for modulating a function of a cell expressing an L-type voltage-gated calcium channel comprising contacting the cell with an antibody, or antigen-binding fragment thereof, which specifically binds to (a) an amino acid sequence of an extracellular domain of a pore loop between transmembrane segments S5 and S6 of domain 1 of an alpha 1 subunit of the L-type voltage-gated calcium channel, or (b) competitively inhibits the binding of (a) to the alpha 1 subunit, wherein binding of the agent to the alpha I subunit modulates the activity of the L-type voltage-gated calcium channel.

### Claim 38 (depends on 37)

The method of claim 37, wherein the antibody or binding fragment thereof is the antibody or binding fragment thereof of any one of the preceding claims.

### Claim 39 (depends on 37, 38)

The method of claim 37 or 38, wherein the cell is a hematopoietic cell.

### Claim 40

The method of any one of the preceding claims, wherein the antibody or antigen binding-fragment thereof inhibits the activity of the L-type voltage-gated calcium channel.

### Claim 41

The method any one of the preceding claims, wherein the antibody or antigen binding-fragment thereof increases the activity of the L-type voltage-gated calcium channel.

### Claim 42 (depends on 39, 40, 41)

The method of any of claims 39-41, wherein the cell is a hematopoietic cell of the lymphoid lineage.

### Claim 43 (depends on 42)

The method of claim 42, wherein the cell is a T cell.

### Claim 44 (depends on 43)

The method of claim 43, wherein the function of the cell comprises T cell maturation.

### Claim 45 (depends on 43)

The method of claim 43, wherein the function of the T cell comprises antigen binding.

### Claim 46 (depends on 42)

The method of claim 42, wherein the cell is a B cell.

### Claim 47 (depends on 46)

The method of claim 46, wherein the function of the cell comprises B cell maturation.

### Claim 48 (depends on 46)

The method of claim 46, wherein the function of the cell comprises B cell receptor-induced activation.

### Claim 49

The method of any one of the preceding claims, wherein the L-type voltage-gated calcium channel is Cav1.4.

### Claim 50

The method of any one of the preceding claims, wherein the L-type voltage-gated calcium channel is Cav1.3.

### Claim 51

The method of any one of the preceding claims, wherein the L-type voltage-gated calcium channel is Cav1.2.

### Claim 52

The method of any one of the preceding claims, wherein the L-type voltage-gated calcium channel is Cav1.1.

### Claim 53

A method of modulating an immune response in a subject comprising administering to the subject an effective amount of an antibody, or antigen-binding fragment thereof, which specifically binds to (a) an amino acid sequence of an extracellular domain of a pore loop between transmembrane segments S5 and S6 of domain 1 of an alpha 1 subunit of the L-type voltage-gated calcium channel, or (b) competitively inhibits the binding of (a) to the alpha 1 subunit, wherein the L-type voltage-gated calcium channel is expressed in a hematopoietic cell.

### Claim 54 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 53)

The method of claim 53, wherein the antibody or binding fragment thereof is the antibody or binding fragment thereof of any of claims 1-10.

### Claim 55 (depends on 53, 54)

The method of claim 53 or 54, wherein the hematopoietic cell is of the lymphoid lineage.

### Claim 56 (depends on 53, 54, 55)

The method of any one of claims 53-55, wherein the hematopoietic cell is a T cell or a B cell.

### Claim 57 (depends on 53, 54, 55, 56)

The method of any one of claims 53-56, wherein the L-type voltage-gated calcium channel is Cav1.4.

### Claim 58 (depends on 53, 54, 55, 56, 57)

The method of any one of claims 53-57, wherein the L-type voltage-gated calcium channel is Cav1.3.

### Claim 59 (depends on 53, 54, 55, 56, 57, 58)

The method of any one of claims 53-58, wherein the L-type voltage-gated calcium channel is Cav1.2.

### Claim 60 (depends on 53, 54, 55, 56, 57, 58, 59)

The method of any one of claims 53-59, wherein the L-type voltage-gated calcium channel is Cav1.1.

### Claim 61

A method of inhibiting an immune response in a subject comprising administering to the subject an effective amount of an antibody, or antigen-binding fragment thereof, which specifically binds to (a) an amino acid sequence of an extracellular domain of a pore loop between transmembrane segments S5 and S6 of domain 1 of an alpha 1 subunit of the L-type voltage-gated calcium channel, or (b) competitively inhibits the binding of (a) to the alpha 1 subunit, wherein the L-type voltage-gated calcium channel is expressed in a hematopoietic cell.

### Claim 62 (depends on 61)

The method of claim 61, wherein the antibody or binding fragment thereof is the antibody or binding fragment thereof of any one of the preceding claims.

### Claim 63 (depends on 61, 62)

The method according to claim 61 or 62, wherein the hematopoietic cell is of the lymphoid lineage.

### Claim 64 (depends on 61, 62, 63)

The method according any one of claims 61-63, wherein the hematopoietic cell is a T cell.

### Claim 65 (depends on 64)

The method of claim 64, wherein the administering the effective amount of the antibody or antigen-binding fragment thereof decreases T cell receptor-induced Ca2+ fluxes.

### Claim 66 (depends on 64)

The method of claim 64, wherein the administering the effective amount of the antibody or antigen-binding fragment thereof reduces naïve T cell survival.

### Claim 67 (depends on 64)

The method of claim 64, wherein the administering the effective amount of the antibody or antigen-binding fragment reduces CD3/CD28 induced T cell proliferation.

### Claim 68 (depends on 61, 62, 63)

The method according any of claims 61-63, wherein the hematopoietic cell is a B cell.

### Claim 69 (depends on 68)

The method of claim 68, wherein the administering the effective amount of the antibody or antigen-binding fragment inhibits B cell receptor-induced activation.

### Claim 70 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69)

The method of any one of claims 61-69, wherein the L-type voltage-gated calcium channel is Cav1.4.

### Claim 71 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The method of any one of claims 61-70, wherein the L-type voltage-gated calcium channel is Cav1.3.

### Claim 72 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71)

The method of any one of claims 61-71, wherein the L-type voltage-gated calcium channel is Cav1.2.

### Claim 73 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)

The method of any one of claims 61-72, wherein the L-type voltage-gated calcium channel is Cav1.1.

### Claim 74

A method of treating a disease in a subject comprising administering to the subject an effective amount of an antibody, or antigen-binding fragment thereof, which specifically binds to (a) an amino acid sequence of an extracellular domain of a pore loop between transmembrane segments S5 and S6 of domain 1 of an alpha 1 subunit of the L-type voltage-gated calcium channel, or (b) competitively inhibits the binding of (a) to the alpha 1 subunit.

### Claim 75 (depends on 74)

The method of claim 74, wherein the antibody or binding fragment thereof is the antibody or binding fragment thereof of any one of the preceding claims.

### Claim 76 (depends on 74, 75)

The method of claim 74 or 75, wherein the disease is an inflammatory disease.

### Claim 77 (depends on 76)

The method of claim 76, wherein the inflammatory disease is X-linked agammaglobulinemia, systemic lupus erythematosus, inflammatory (rheumatoid) arthritis, Hashimoto's thyroiditis, pernicious anemia, inflammatory bowel disease (Crohn's disease and ulcerative colitis), psoriasis, renal fibroses, pulmonary fibroses, hepatic fibroses, Addison's disease, Type I diabetes, systemic lupus erythematosus (SLE), dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, Reiter's syndrome, asthma, or Grave's disease.

### Claim 78 (depends on 74, 75)

The method of claim 74 or 75, wherein the disease is a cancer.

### Claim 79 (depends on 78)

The method of claim 78, wherein the cancer is a hematopoietic cancer.

### Claim 80 (depends on 79)

The method of claim 79, wherein hematopoietic cancer is a lymphoma, leukemia, or multiple myeloma.

### Claim 81 (depends on 80)

The method of claim 80, wherein the lymphoma is a T-cell lymphoma, B-cell lymphoma, small lymphocytic lymphoma, mangle cell lymphoma, anaplastic large cell lymphoma (ALCL), follicular lymphoma, Hodgkin's lymphoma, or non-Hodgkin's lymphoma.

### Claim 82 (depends on 80)

The method of claim 80, wherein the leukemia is chronic lymphocytic leukemia (CLL), hairy cell leukemia, acute lymphoblastic leukemia, myelocytic leukemia, acute myeloid or myelogenous leukemia, or chronic myelogenous leukemia.

### Claim 83 (depends on 78)

The method of claim 78, wherein the cancer is selected from one or more of breast cancer, cervical cancer, prostate cancer, gastrointestinal cancer, lung cancer, ovarian cancer, testicular cancer, head and neck cancer, bladder cancer, kidney cancer (e.g., renal cell carcinoma), soft tissue sarcoma, squamous cell carcinoma, CNS or brain cancer, melanoma, non-melanoma cancer, thyroid cancer, endometrial cancer, an epithelial tumor, and bone cancer.

### Claim 84 (depends on 74, 75, 76, 77, 78, 79, 80, 81, 82, 83)

The method of any one of claims 74-83, wherein the cancer expresses or overexpresses Cav1.1, Cav1.2, Cav1.3, Cav1.4, or any combination thereof.

### Claim 85 (depends on 84)

The method of claim 84, wherein the cancer expresses or overexpresses Cav1.1 and the antibody, or antigen-binding fragment thereof, specifically binds to Cav1.1.

### Claim 86 (depends on 84)

The method of claim 84, wherein the cancer expresses or overexpresses Cav1.2 and the antibody, or antigen-binding fragment thereof, specifically binds to Cav1.2.

### Claim 87 (depends on 84)

The method of claim 84, wherein the cancer expresses or overexpresses Cav1.3 and the antibody, or antigen-binding fragment thereof, specifically binds to Cav1.3.

### Claim 88 (depends on 84)

The method of claim 84, wherein the cancer expresses or overexpresses Cav1.4 and the antibody, or antigen-binding fragment thereof, specifically binds to Cav1.4.