IP Library › Granted Patent US 12,331,111
Granted Patent B2
US 12,331,111 · App. 17/821,006 · Granted Jun 17, 2025

Anti-MS4A4A antibodies and methods of use thereof

Inventors: Philip Kong (San Francisco, CA); Herve Rhinn (San Francisco, CA); Tina Schwabe (San Francisco, CA); Angie Yee (San Francisco, CA); Ilaria Tassi (San Francisco, CA); Muhammad Abbas Alhawagri (San Francisco, CA); Arnon Rosenthal (Woodside, CA)
Assignee: Alector LLC
C07K16/28C07K2317/24C07K2317/31C07K2317/71
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Patent No.
US 12,331,111
App. No.
17/821,006
Granted
Jun 17, 2025
Kind
B2
Abstract

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, antibodies, antibody fragments, etc., that specifically bind a MS4A4A polypeptide, e.g., a mammalian MS4A4A or human MS4A4A, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Claims (27)

1. A method of treating an individual having Alzheimer's disease, late onset Alzheimer's disease, or cognitive impairment, the method comprising administering to an individual in need thereof a therapeutically effective amount of an isolated antibody that binds to human MS4A4A, wherein the antibody comprises a heavy chain variable region and a light chain variable region,

wherein the heavy chain variable region and the light chain variable region comprise an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 4, 20, 38, 56, 75, and 86, respectively; SEQ ID NOs: 5, 21, 39, 57, 76, and 87, respectively; SEQ ID NOs: 6, 22, 40, 58, 76, and 88, respectively; SEQ ID NOs: 7, 23, 41, 59, 77, and 89, respectively; SEQ ID NOs: 8, 24, 42, 60, 78, and 90, respectively; SEQ ID NOs: 9, 25, 43, 61, 76, and 91, respectively; SEQ ID NOs: 10, 26, 44, 62, 79, and 93, respectively; SEQ ID NOs: 7, 27, 45, 63, 77, and 89, respectively; SEQ ID NOs: 7, 28, 46, 64, 77, and 89, respectively; SEQ ID NOs: 11, 29, 47, 65, 80, and 93, respectively; SEQ ID NOs: 12, 27, 45, 66, 77, and 89, respectively; SEQ ID NOs: 13, 30, 48, 67, 76, and 94, respectively; SEQ ID NOs: 14, 31, 49, 68, 81, and 95, respectively; SEQ ID NOs: 16, 33, 51, 70, 77, and 97, respectively; SEQ ID NOs: 17, 34, 52, 71, 83, and 98, respectively; SEQ ID NOs: 19, 36, 54, 73, 84, and 100, respectively; SEQ ID NOs: 7, 37, 55, 74, 85, and 89, respectively; SEQ ID NOs: 142, 154, 168, 183, 197, and 210 respectively; SEQ ID NOs: 144, 156, 170, 185, 199, and 212, respectively; SEQ ID NOs: 144, 157, 171, 186, 81, and 213, respectively; SEQ ID NOs: 145, 158, 172, 186, 81, and 214, respectively; SEQ ID NOs: 146, 159, 173, 187, 200, and 215, respectively; SEQ ID NOs: 147, 160, 174, 188, 201, and 216, respectively; SEQ ID NOs: 148, 161, 175, 189, 202, and 217, respectively; SEQ ID NOs: 149, 162, 176, 190, 203, and 218, respectively; SEQ ID NOs: 150, 163, 177, 191, 204, and 219, respectively; SEQ ID NOs: 151, 164, 178, 192, 205, and 220, respectively; SEQ ID NOs: 147, 160, 179, 193, 206, and 221, respectively; SEQ ID NOs: 152, 165, 180, 194, 207, and 222, respectively; SEQ ID NOs: 153, 166, 181, 195, 208, and 223, respectively; SEQ ID NOs: 151, 167, 182, 196, 209, and 224, respectively; SEQ ID NOs: 304, 310, 316, 322, 328, and 334, respectively; SEQ ID NOs: 305, 311, 317, 323, 329, and 335, respectively; SEQ ID NOs: 306, 312, 318, 324, 330, and 336, respectively; SEQ ID NOs: 307, 313, 319, 325, 331, and 337, respectively; SEQ ID NOs: 308, 314, 320, 326, 332, and 338, respectively; SEQ ID NOs: 309, 315, 321, 327, 333, and 339, respectively; SEQ ID NOs: 15, 32, 50, 69, 82, and 96, respectively; SEQ ID NOs: 18, 35, 53, 72, 77, and 99, respectively; and SEQ ID NOs: 143, 155, 169, 184, 198, and 211, respectively.

2. A method of treating an individual with over expression or increased activity of MS4A4A, the method comprising administering to an individual in need thereof a therapeutically effective amount of an isolated antibody that binds to human MS4A4A, wherein the antibody comprises a heavy chain variable region and a light chain variable region,

wherein the heavy chain variable region and the light chain variable region comprise an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 4, 20, 38, 56, 75, and 86, respectively; SEQ ID NOs: 5, 21, 39, 57, 76, and 87, respectively; SEQ ID NOs: 6, 22, 40, 58, 76, and 88, respectively; SEQ ID NOs: 7, 23, 41, 59, 77, and 89, respectively; SEQ ID NOs: 8, 24, 42, 60, 78, and 90, respectively; SEQ ID NOs: 9, 25, 43, 61, 76, and 91, respectively; SEQ ID NOs: 10, 26, 44, 62, 79, and 93, respectively; SEQ ID NOs: 7, 27, 45, 63, 77, and 89, respectively; SEQ ID NOs: 7, 28, 46, 64, 77, and 89, respectively; SEQ ID NOs: 11, 29, 47, 65, 80, and 93, respectively; SEQ ID NOs: 12, 27, 45, 66, 77 and 89, respectively; SEQ ID NOs: 13, 30, 48, 67, 76, and 94, respectively; SEQ ID NOs: 14, 31, 49, 68, 81, and 95, respectively; SEQ ID NOs: 16, 33, 51, 70, 77, and 97, respectively; SEQ ID NOs: 17, 34, 52, 71, 83, and 98, respectively; SEQ ID NOs: 19, 36, 54, 73, 84, and 100, respectively; SEQ ID NOs: 7, 37, 55, 74, 85, and 89, respectively; SEQ ID NOs: 142, 154, 168, 183, 197, and 210, respectively; SEQ ID NOs: 144, 156, 170, 185, 199, and 212, respectively; SEQ ID NOs: 144, 157, 171, 186, 81, and 213, respectively; SEQ ID NOs: 145, 158, 172, 186, 81, and 214, respectively; SEQ ID NOs: 146, 159, 173, 187, 200, and 215, respectively; SEQ ID NOs: 147, 160, 174, 188, 201, and 216, respectively; SEQ ID NOs: 148, 161, 175, 189, 202, and 217, respectively; SEQ ID NOs: 149, 162, 176, 190, 203, and 218, respectively; SEQ ID NOs: 150, 163, 177, 191, 204, and 219, respectively; SEQ ID NOs: 151, 164, 178, 192, 205, and 220, respectively; SEQ ID NOs: 147, 160, 179, 193, 206, and 221, respectively; SEQ ID NOs: 152, 165, 180, 194, 207, and 222, respectively; SEQ ID NOs: 153, 166, 181, 195, 208, and 223, respectively; SEQ ID NOs: 151, 167, 182, 196, 209, and 224, respectively; SEQ ID NOs: 304, 310, 316, 322, 328, and 334, respectively; SEQ ID NOs: 305, 311, 317, 323, 329, and 335, respectively; SEQ ID NOs: 306, 312, 318, 324, 330, and 336, respectively; SEQ ID NOs: 307, 313, 319, 325, 331, and 337, respectively; SEQ ID NOs: 308, 314, 320, 326, 332, and 338, respectively; SEQ ID NOs: 309, 315, 321, 327, 333, and 339, respectively; SEQ ID NOs: 15, 32, 50, 69, 82, and 96, respectively; SEQ ID NOs: 18, 35, 53, 72, 77, and 99, respectively; and SEQ ID NOs: 143, 155, 169, 184, 198, and 211, respectively.

3. A method of treating an individual having mild cognitive impairment, the method comprising administering to an individual in need thereof a therapeutically effective amount of an isolated antibody that binds to human MS4A4A, wherein the antibody comprises a heavy chain variable region and a light chain variable region,

wherein the heavy chain variable region and the light chain variable region comprise an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 4, 20, 38, 56, 75, and 86, respectively; SEQ ID NOs: 5, 21, 39, 57, 76, and 87, respectively; SEQ ID NOs: 6, 22, 40, 58, 76, and 88, respectively; SEQ ID NOs: 7, 23, 41, 59, 77, and 89, respectively; SEQ ID NOs: 8, 24, 42, 60, 78, and 90, respectively; SEQ ID NOs: 9, 25, 43, 61, 76, and 91, respectively; SEQ ID NOs: 10, 26, 44, 62, 79, and 93, respectively; SEQ ID NOs: 7, 27, 45, 63, 77, and 89, respectively; SEQ ID NOs: 7, 28, 46, 64, 77, and 89, respectively; SEQ ID NOs: 11, 29, 47, 65, 80, and 93, respectively; SEQ ID NOs: 12, 27, 45, 66, 77, and 89, respectively; SEQ ID NOs: 13, 30, 48, 67, 76, and 94, respectively; SEQ ID NOs: 14, 31, 49, 68, 81, and 95, respectively; SEQ ID NOs: 16, 33, 51, 70, 77, and 97, respectively; SEQ ID NOs: 17, 34, 52, 71, 83, and 98, respectively; SEQ ID NOs: 19, 36, 54, 73, 84, and 100, respectively; SEQ ID NOs: 7, 37, 55, 74, 85, and 89, respectively; SEQ ID NOs: 142, 154, 168, 183, 197, and 210, respectively; SEQ ID NOs: 144, 156, 170, 185, 199, and 212, respectively; SEQ ID NOs: 144, 157, 171, 186, 81, and 213, respectively; SEQ ID NOs: 145, 158, 172, 186, 81, and 214, respectively; SEQ ID NOs: 146, 159, 173, 187, 200, and 215, respectively; SEQ ID NOs: 147, 160, 174, 188, 201, and 216, respectively; SEQ ID NOs: 148, 161, 175, 189, 202, and 217, respectively; SEQ ID NOs: 149, 162, 176, 190, 203, and 218, respectively; SEQ ID NOs: 150, 163, 177, 191, 204, and 219, respectively; SEQ ID NOs: 151, 164, 178, 192, 205, and 220, respectively; SEQ ID NOs: 147, 160, 179, 193, 206, and 221, respectively; SEQ ID NOs: 152, 165, 180, 194, 207, and 222, respectively; SEQ ID NOs: 153, 166, 181, 195, 208, and 223, respectively; SEQ ID NOs: 151, 167, 182, 196, 209, and 224, respectively; SEQ ID NOs: 304, 310, 316, 322, 328, and 334, respectively; SEQ ID NOs: 305, 311, 317, 323, 329, and 335, respectively; SEQ ID NOs: 306, 312, 318, 324, 330, and 336, respectively; SEQ ID NOs: 307, 313, 319, 325, 331, and 337, respectively; SEQ ID NOs: 308, 314, 320, 326, 332, and 338, respectively; SEQ ID NOs: 309, 315, 321, 327, 333, and 339, respectively; SEQ ID NOs: 15, 32, 50, 69, 82, and 96, respectively; SEQ ID NOs: 18, 35, 53, 72, 77, and 99, respectively; and SEQ ID NOs: 143, 155, 169, 184, 198, and 211, respectively.

4. The method of claim 1 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences selected from the group consisting of SEQ ID NOs: 101 and 121, respectively; SEQ ID NOs: 102 and 122, respectively; SEQ ID NOs: 103 and 123, respectively; SEQ ID NOs: 104 and 124, respectively; SEQ ID NOs: 105 and 125, respectively; SEQ ID NOs: 106 and 126, respectively; SEQ ID NOs: 107 and 127, respectively; SEQ ID NOs: 108 and 128, respectively; SEQ ID NOs: 109 and 129, respectively; SEQ ID NOs: 110 and 130, respectively; SEQ ID NOs: 111 and 131, respectively; SEQ ID NOs: 112 and 132, respectively; SEQ ID NOs: 113 and 128, respectively; SEQ ID NOs: 114 and 133, respectively; SEQ ID NOs: 115 and 134, respectively; SEQ ID NOs: 116 and 135, respectively; SEQ ID NOs: 117 and 136, respectively; SEQ ID NOs: 118 and 137, respectively; SEQ ID NOs: 119 and 138, respectively; SEQ ID NOs: 120 and 139, respectively; SEQ ID NOs: 225 and 240, respectively; SEQ ID NOs: 226 and 241, respectively; SEQ ID NOs: 227 and 242, respectively; SEQ ID NOs: 228 and 243, respectively; SEQ ID NOs: 229 and 244, respectively; SEQ ID NOs: 230 and 245, respectively; SEQ ID NOs: 231 and 246, respectively; SEQ ID NOs: 232 and 247, respectively; SEQ ID NOs: 233 and 248, respectively; SEQ ID NOs: 234 and 249, respectively; SEQ ID NOs: 235 and 250, respectively; SEQ ID NOs: 236 and 251, respectively; SEQ ID NOs: 237 and 252, respectively; SEQ ID NOs: 238 and 253, respectively; SEQ ID NOs: 239 and 254, respectively; SEQ ID NOs: 340 and 346, respectively; SEQ ID NOs: 341 and 347, respectively; SEQ ID NOs: 342 and 348, respectively; SEQ ID NOs: 343 and 349, respectively; SEQ ID NOs: 344 and 350, respectively; and SEQ ID NOs: 345 and 351, respectively.

5. The method of claim 2 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences selected from the group consisting of SEQ ID NOs: 101 and 121, respectively; SEQ ID NOs: 102 and 122, respectively; SEQ ID NOs: 103 and 123, respectively; SEQ ID NOs: 104 and 124, respectively; SEQ ID NOs: 105 and 125, respectively; SEQ ID NOs: 106 and 126, respectively; SEQ ID NOs: 107 and 127, respectively; SEQ ID NOs: 108 and 128, respectively; SEQ ID NOs: 109 and 129, respectively; SEQ ID NOs: 110 and 130, respectively; SEQ ID NOs: 111 and 131, respectively; SEQ ID NOs: 112 and 132, respectively; SEQ ID NOs: 113 and 128, respectively; SEQ ID NOs: 114 and 133, respectively; SEQ ID NOs: 115 and 134, respectively; SEQ ID NOs: 116 and 135, respectively; SEQ ID NOs: 117 and 136, respectively; SEQ ID NOs: 118 and 137, respectively; SEQ ID NOs: 119 and 138, respectively; SEQ ID NOs: 120 and 139, respectively; SEQ ID NOs: 225 and 240, respectively; SEQ ID NOs: 226 and 241, respectively; SEQ ID NOs: 227 and 242, respectively; SEQ ID NOs: 228 and 243, respectively; SEQ ID NOs: 229 and 244, respectively; SEQ ID NOs: 230 and 245, respectively; SEQ ID NOs: 231 and 246, respectively; SEQ ID NOs: 232 and 247, respectively; SEQ ID NOs: 233 and 248, respectively; SEQ ID NOs: 234 and 249, respectively; SEQ ID NOs: 235 and 250, respectively; SEQ ID NOs: 236 and 251, respectively; SEQ ID NOs: 237 and 252, respectively; SEQ ID NOs: 238 and 253, respectively; SEQ ID NOs: 239 and 254, respectively; SEQ ID NOs: 340 and 346, respectively; SEQ ID NOs: 341 and 347, respectively; SEQ ID NOs: 342 and 348, respectively; SEQ ID NOs: 343 and 349, respectively; SEQ ID NOs: 344 and 350, respectively; and SEQ ID NOs: 345 and 351, respectively.

6. The method of claim 3 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences selected from the group consisting of SEQ ID NOs: 101 and 121, respectively; SEQ ID NOs: 102 and 122, respectively; SEQ ID NOs: 103 and 123, respectively; SEQ ID NOs: 104 and 124, respectively; SEQ ID NOs: 105 and 125, respectively; SEQ ID NOs: 106 and 126, respectively; SEQ ID NOs: 107 and 127, respectively; SEQ ID NOs: 108 and 128, respectively; SEQ ID NOs: 109 and 129, respectively; SEQ ID NOs: 110 and 130, respectively; SEQ ID NOs: 111 and 131, respectively; SEQ ID NOs: 112 and 132, respectively; SEQ ID NOs: 113 and 128, respectively; SEQ ID NOs: 114 and 133, respectively; SEQ ID NOs: 115 and 134, respectively; SEQ ID NOs: 116 and 135, respectively; SEQ ID NOs: 117 and 136, respectively; SEQ ID NOs: 118 and 137, respectively; SEQ ID NOs: 119 and 138, respectively; SEQ ID NOs: 120 and 139, respectively; SEQ ID NOs: 225 and 240, respectively; SEQ ID NOs: 226 and 241, respectively; SEQ ID NOs: 227 and 242, respectively; SEQ ID NOs: 228 and 243, respectively; SEQ ID NOs: 229 and 244, respectively; SEQ ID NOs: 230 and 245, respectively; SEQ ID NOs: 231 and 246, respectively; SEQ ID NOs: 232 and 247, respectively; SEQ ID NOs: 233 and 248, respectively; SEQ ID NOs: 234 and 249, respectively; SEQ ID NOs: 235 and 250, respectively; SEQ ID NOs: 236 and 251, respectively; SEQ ID NOs: 237 and 252, respectively; SEQ ID NOs: 238 and 253, respectively; SEQ ID NOs: 239 and 254, respectively; SEQ ID NOs: 340 and 346, respectively; SEQ ID NOs: 341 and 347, respectively; SEQ ID NOs: 342 and 348, respectively; SEQ ID NOs: 343 and 349, respectively; SEQ ID NOs: 344 and 350, respectively; and SEQ ID NOs: 345 and 351, respectively.

7. The method of claim 1 , wherein the antibody is a murine antibody, a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody.

8. The method of claim 1 , wherein the antibody is of the IgG class, the IgM class, or the IgA class.

9. The method of claim 8 , wherein the antibody is of the IgG class and has an IgG1, IgG2, or IgG4 isotype.

10. The method of claim 1 , wherein the antibody is an antibody fragment.

11. The method of claim 10 , wherein the fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.

12. The method of claim 1 , wherein the antibody further comprises an antigen facilitating transport across the blood brain barrier, wherein the antigen facilitating transport across the blood brain selected is from the group consisting of transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low density lipoprotein receptor related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, a llama single domain antibody, TMEM 30(A), a protein transduction domain, TAT, Syn-B, penetratin, a poly-arginine peptide, an angiopeptide, basigin, Glut1, CD98hc, and ANG1005.

13. The method of claim 2 , wherein the antibody is a murine antibody, a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody.

14. The method of claim 2 , wherein the antibody is of the IgG class, the IgM class, or the IgA class.

15. The method of claim 14 , wherein the antibody is of the IgG class and has an IgG1, IgG2, or IgG4 isotype.

16. The method of claim 2 , wherein the antibody is an antibody fragment.

17. The method of claim 16 , wherein the fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.

18. The method of claim 2 , wherein the antibody further comprises an antigen facilitating transport across the blood brain barrier, wherein the antigen facilitating transport across the blood brain selected is from the group consisting of transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low density lipoprotein receptor related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, a llama single domain antibody, TMEM 30(A), a protein transduction domain, TAT, Syn-B, penetratin, a poly-arginine peptide, an angiopeptide, basigin, Glut1, CD98hc, and ANG1005.

19. The method of claim 3 , wherein the antibody is a murine antibody, a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody.

20. The method of claim 3 , wherein the antibody is of the IgG class, the IgM class, or the IgA class.

21. The method of claim 20 , wherein the antibody is of the IgG class and has an IgG1, IgG2, or IgG4 isotype.

22. The method of claim 3 , wherein the antibody is an antibody fragment.

23. The method of claim 22 , wherein the fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.

24. The method of claim 3 , wherein the antibody further comprises an antigen facilitating transport across the blood brain barrier, wherein the antigen facilitating transport across the blood brain selected is from the group consisting of transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low density lipoprotein receptor related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, a llama single domain antibody, TMEM 30(A), a protein transduction domain, TAT, Syn-B, penetratin, a poly-arginine peptide, an angiopeptide, basigin, Glut1, CD98hc, and ANG1005.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2025
From: KONG, PHILIP; RHINN, HERVE; SCHWABE, TINA; YEE, ANGIE; ROSENTHAL, ARNON
To: ALECTOR LLC
Reel/Frame 070635/0074 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2025
From: KONG, PHILIP; RHINN, HERVE; SCHWABE, TINA; YEE, ANGIE; ROSENTHAL, ARNON
To: ALECTOR LLC
Reel/Frame 070635/0193 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2025
From: TASSI, ILARIA; ALHAWAGRI, MUHAMMAD ABBAS
To: ALECTOR LLC
Reel/Frame 070635/0271 →
CHANGE OF ADDRESS Recorded Mar 26, 2025
From: ALECTOR LLC
To: ALECTOR LLC
Reel/Frame 070643/0826 →
SECURITY INTEREST Recorded Nov 14, 2024
From: ALECTOR, INC.; ALECTOR LLC
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 069386/0141 →
Continuity (4)
Division 16965676
Provisional Application 62783096 · Dec 20, 2018
Provisional Application 62624600 · Jan 31, 2018
Related Publication 20230126400A1 · Apr 27, 2023
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