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US 11,628,224 B2Granted
Therapeutic agents targeting CLPTM1
AssigneeGenagon Therapeutics AB
InventorsJohan Erik Simon Fredriksson, Olof Andries Blokzijl
Life of this patent
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Abstract
A therapeutic agent capable of binding to the receptor CLPTM1 at the surface of an immune cell and modulating its activity for use in modulating the activity of the immune system to treat cancer, wherein the therapeutic agent is capable of inhibiting the growth and/or viability of an anti-inflammatory and/or immunosuppressive cell to relieve unwanted or deleterious immunosuppression by eliminating anti-inflammatory and/or immunosuppressive immune cells; and/or the therapeutic agent is capable of stimulating an antigen-presenting immune cell and acts to stimulate antigen-presenting immune cells to activate an anti-cancer immune response.
Claims24
A product comprising:
- (a) a therapeutic agent capable of binding to CLPTM1 at the surface of a cell and inhibiting the growth and/or viability of said cell;
- and
- (b) an immune checkpoint inhibitor, the immune checkpoint inhibitor being an antibody which binds to an immune checkpoint protein or to a receptor for an immune checkpoint protein;
- wherein said therapeutic agent and said immune checkpoint inhibitor are formulated for combined administration separately, sequentially or simultaneously, and wherein the therapeutic agent is selected from:
- (i) an antibody having immune effector function selected from antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cell-mediated phagocytosis (ADCP), and/or complement dependent cytotoxicity (CDC);
- and
- (ii) a conjugate comprising an antibody conjugated to a cytotoxic or cytostatic drug, wherein said antibody is capable of being internalized by the cell,
- wherein said antibody in said therapeutic agent is capable of binding to CLPTM1 and comprises the complementarity-determining regions (CDRs) VLCDR1, VLCDR2, VLCDR3, VHCDR1, VHCDR2 and VHCDR3, and wherein
- (i) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 66;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 67;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 68;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 69;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 70;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 71;
- or
- (ii) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 72;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 73;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 74;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 75;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 76;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 77.
34 more elements
A therapeutic agent capable of binding to CLPTM1 at the surface of an immune cell and modulating its activity, wherein
- (i) the therapeutic agent is capable of inhibiting the growth and/or viability of an anti-inflammatory and/or immunosuppressive cell;
- and/or
- (ii) the therapeutic agent is capable of stimulating an antigen-presenting immune cell;
- wherein each said therapeutic agent (i) and (ii) is a conjugate comprising an antibody capable of binding to CLPTM1, conjugated to a drug;
- and
- wherein said antibody comprises the complementarity-determining regions (CDRs) VLCDR1, VLCDR2, VLCDR3, VHCDR1, VHCDR2 and VHCDR3, wherein
- (i) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 66;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 67;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 68;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 69;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 70;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 71;
- or
- (ii) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 72;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 73;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 74;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 75;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 76;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 77.
32 more elements
A product comprising:
- (a) a therapeutic agent capable of binding to CLPTM1 at the surface of antigen-presenting cells (APC) selected from dendritic cells and macrophage cells and stimulating said APC to activate an immune response;
- and
- (b) an immune checkpoint inhibitor, being an antibody which binds to an immune checkpoint protein, or to a receptor for an immune checkpoint protein;
- wherein said therapeutic agent and said immune checkpoint inhibitor are formulated for combined administration separately, sequentially or simultaneously;
- and wherein the therapeutic agent is an antibody-drug conjugate (ADC) wherein the drug comprises a tubulin inhibitor and the antibody is capable of binding specifically to CLPTM1 and comprises the complementarity-determining regions (CDRs) VLCDR1, VLCDR2, VLCDR3, VHCDR1, VHCDR2 and VHCDR3, wherein
- (i) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 66;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 67;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 68;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 69;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 70;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 71;
- or
- (ii) each of said CDRs has an amino acid sequence as follows:
- VLCDR1 has the sequence set forth in SEQ ID NO:
- 72;
- VLCDR2 has the sequence set forth in SEQ ID NO:
- 73;
- VLCDR3 has the sequence set forth in SEQ ID NO:
- 74;
- VHCDR1 has the sequence set forth in SEQ ID NO:
- 75;
- VHCDR2 has the sequence set forth in SEQ ID NO:
- 76;
- and
- VHCDR3 has the sequence set forth in SEQ ID NO:
- 77.
31 more elements
Dependencies are inferred from the claim text.