IP Library › Granted Patent US 12,319,734
Granted Patent B2
US 12,319,734 · App. 17/820,686 · Granted Jun 3, 2025

Anti-TMEM106B antibodies and methods of use thereof

Inventors: Arnon Rosenthal (Woodside, CA); Eric Brown (South San Francisco, CA); Tina Schwabe (San Francisco, CA); Angie Yee (San Francisco, CA); Herve Rhinn (San Francisco, CA)
Assignee: ALECTOR LLC
C07K16/28C07K2317/34C07K2317/56
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Quick Facts
Patent No.
US 12,319,734
App. No.
17/820,686
Granted
Jun 3, 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 TMEM106B polypeptide, e.g., a mammalian TMEM106B or human TMEM106B, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Claims (97)

1. An isolated nucleic acid comprising a nucleic acid sequence encoding an antibody that binds to human TMEM106B, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and light chain variable region comprise:

(a) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 4, 37, 80, 122, 162, and 187, respectively;

(b) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 5, 38, 81, 123, 163, and 188, respectively;

(c) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 11, 44, 87, 123, 169, and 188, respectively;

(d) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 12, 45, 88, 129, 170, and 194, respectively;

(e) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 13, 46, 89, 130, 171, and 195, respectively;

(f) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 14, 47, 90, 131, 170, and 196, respectively;

(g) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 15, 48, 91, 132, 172, and 197, respectively;

(h) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 6, 53, 96, 136, 175, and 201, respectively;

(i) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 14, 54, 97, 137, 176, and 202, respectively;

(i) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 19, 55, 98, 138, 169, and 203, respectively;

(k) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 11, 58, 101, 138, 169, and 207, respectively;

(l) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 14, 64, 107, 146, 161, and 202, respectively;

(m) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 25, 67, 110, 149, 161, and 196, respectively;

(n) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 26, 68, 111, 150, 181, and 214, respectively;

(o) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 27, 69, 112, 151, 181, and 215, respectively;

(p) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 29, 71, 111, 153, 181, and 214, respectively;

(g) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 33, 75, 117, 156, 161, and 220, respectively;

(r) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 9, 42, 85, 127, 167, and 192, respectively;

(s) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 7, 40, 83, 125, 165, and 190, respectively;

(t) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 9, 60, 103, 143, 167, and 192, respectively;

(u) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 21, 61, 104, 144, 169, and 209, respectively;

(v) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 16, 50, 93, 134, 172, and 199, respectively; or

(w) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 13, 46, 89, 141, 171, and 206, respectively; or

(x) an HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 62, 105, 145, 161, and 210, respectively.

2. A vector comprising the nucleic acid of claim 1 .

3. An isolated host cell comprising the vector of claim 2 .

4. A method of producing an antibody that binds to human TMEM106B, comprising culturing the cell of claim 3 so that the antibody is produced.

5. The method of claim 4 , further comprising recovering the antibody produced by the cell.

6. The nucleic acid of claim 1 , wherein the heavy chain variable region and light chain variable region comprise the amino acid sequences of:

(a) SEQ ID NOs: 226 and 270, respectively;

(b) SEQ ID NOs: 227 and 271, respectively;

(c) SEQ ID NOs: 233 and 277, respectively;

(d) SEQ ID NOs: 234 and 278, respectively;

(e) SEQ ID NOs: 235 and 279, respectively;

(f) SEQ ID NOs: 236 and 280, respectively;

(g) SEQ ID NOs: 237 and 281, respectively;

(h) SEQ ID NOs: 242 and 286, respectively;

(i) SEQ ID NOs: 243 and 287, respectively;

(j) SEQ ID NOs: 244 and 289, respectively;

(k) SEQ ID NOs: 247 and 293, respectively;

(l) SEQ ID NOs: 253 and 299, respectively;

(m) SEQ ID NOs: 256 and 302, respectively;

(n) SEQ ID NOs: 257 and 303, respectively;

(o) SEQ ID NOs: 258 and 304, respectively;

(p) SEQ ID NOs: 260 and 306, respectively;

(q) SEQ ID NOs: 264 and 310, respectively;

(r) SEQ ID NOs: 231 and 275, respectively;

(s) SEQ ID NOs: 229 and 273, respectively;

(t) SEQ ID NOs: 249 and 295, respectively;

(u) SEQ ID NOs: 250 and 296, respectively;

(v) SEQ ID NOs: 239 and 283, respectively;

(w) SEQ ID NOs: 235 and 292, respectively; or

(x) SEQ ID NOs: 251 and 297, respectively.

7. The nucleic acid of claim 1 , wherein the antibody is a monoclonal antibody.

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

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

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

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

12. The nucleic acid of claim 1 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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 nucleic acid of claim 1 , wherein the heavy chain variable region comprises:

an HVR-H1 comprising the amino acid sequence of SEQ ID NO:11;

an HVR-H2 comprising the amino acid sequence of SEQ ID NO:44; and

an HVR-H3 comprising the amino acid sequence of SEQ ID NO:87; and

wherein the light chain variable region comprises:

an HVR-L1 comprising the amino acid sequence of SEQ ID NO:123;

an HVR-L2 comprising the amino acid sequence of SEQ ID NO:169; and

an HVR-L3 comprising the amino acid sequence of SEQ ID NO:188.

14. The nucleic acid of claim 13 , wherein the heavy chain variable region and light chain variable region comprise the amino acid sequences of SEQ ID NOs: 233 and 277, respectively.

15. The nucleic acid of claim 14 , wherein the antibody is of the IgG class and has an IgG1 isotype.

16. The nucleic acid of claim 13 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected from the group consisting of transferring 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.

17. The nucleic acid of claim 14 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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.

18. The nucleic acid of claim 1 , wherein the heavy chain variable region comprises:

an HVR-H1 comprising the amino acid sequence of SEQ ID NO:5;

an HVR-H2 comprising the amino acid sequence of SEQ ID NO:38; and

an HVR-H3 comprising the amino acid sequence of SEQ ID NO:81; and

wherein the light chain variable region comprises:

an HVR-L1 comprising the amino acid sequence of SEQ ID NO:123;

an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 163; and

an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 188.

19. The nucleic acid of claim 18 , wherein the heavy chain variable region and light chain variable region comprise the amino acid sequences of SEQ ID NOs: 227 and 271, respectively.

20. The nucleic acid of claim 19 , wherein the antibody is of the IgG class and has an IgG1 isotype.

21. The nucleic acid of claim 18 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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.

22. The nucleic acid of claim 19 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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.

23. The nucleic acid of claim 1 ,

wherein the heavy chain variable region comprises:

an HVR-H1 comprising the amino acid sequence of SEQ ID NO:11;

an HVR-H2 comprising the amino acid sequence of SEQ ID NO:58; and

an HVR-H3 comprising the amino acid sequence of SEQ ID NO:101; and

wherein the light chain variable region comprises:

an HVR-L1 comprising the amino acid sequence of SEQ ID NO:138;

an HVR-L2 comprising the amino acid sequence of SEQ ID NO:169; and

an HVR-L3 comprising the amino acid sequence of SEQ ID NO:207.

24. The nucleic acid of claim 23 , wherein the heavy chain variable region and light chain variable region comprise the amino acid sequences of SEQ ID NOs: 247 and 293, respectively.

25. The nucleic acid of claim 24 , wherein the antibody is of the IgG class and has an IgG1 isotype.

26. The nucleic acid of claim 23 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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.

27. The nucleic acid of claim 24 , wherein the antibody further comprises an antigen facilitating transport across the blood-brain-barrier selected 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 (3)
CHANGE OF ADDRESS Recorded Feb 25, 2025
From: ALECTOR LLC
To: ALECTOR LLC
Reel/Frame 070322/0108 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 25, 2025
From: ROSENTHAL, ARNON; BROWN, ERIC; SCHWABE, TINA; YEE, ANGIE; RHINN, HERVE
To: ALECTOR LLC
Reel/Frame 070323/0525 →
SECURITY INTEREST Recorded Nov 14, 2024
From: ALECTOR, INC.; ALECTOR LLC
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 069386/0141 →
Continuity (3)
Division 16959081
Provisional Application 62612098 · Dec 29, 2017
Related Publication 20230303681A1 · Sep 28, 2023
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