IP Library › Granted Patent US 12,258,398

Granted Patent B2

US 12,258,398 · App. 17/263,534 · Granted Mar 25, 2025

Anti-Siglec-5 antibodies and methods of use thereof

Inventors: Patricia Culp (Oakland, CA); Rashmi Bankoti (San Mateo, CA); Helen Lam (Union City, CA); Arnon Rosenthal (Woodside, CA)

Assignee: ALECTOR LLC

C07K16/2803 A61K47/6849 A61P35/00 A61K2039/505 C07K2317/20 C07K2317/21 C07K2317/24 C07K2317/31 C07K2317/33 C07K2317/34 C07K2317/52 C07K2317/522 C07K2317/56 C07K2317/567 C07K2317/76 C07K2317/92

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Quick Facts

Patent No.: US 12,258,398
App. No.: 17/263,534
Granted: Mar 25, 2025
Kind: B2

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Abstract

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind a Siglec-5 protein, e.g., human Siglec-5, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Claims (99)

1. An isolated monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain comprises an HVR-L1, an HVR-L2, and an HVR-L3, and the heavy chain variable domain comprises an HVR-H1, an HVR-H2, and an HVR-H3, wherein:

(a) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 127, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 153, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 20, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 39, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 70;

(b) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 104, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 128, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 154, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 21, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 40, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 71;

(c) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 133, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 161, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 26, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 46, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 77;

(d) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 114, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 127, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 153, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 20, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 49, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 70;

(e) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 115, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 128, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 154, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 21, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 50, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 71; or

(f) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 133, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 161, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 26, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 51, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 77.

2. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody comprises:

a) a light chain variable domain comprising an amino acid sequence of SEQ ID NOs: 194; and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NOs: 174;

b) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 195 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 175;

c) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 202 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 181;

d) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 205 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 184 or 185 or 186;

e) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 206 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 184, 185 or 186;

f) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 207 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 187, 188, 189, or 190;

g) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 208 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 187, 188, 189 or 190;

h) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 209 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 191, 192 or 193;

i) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 210 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 191, 192 or 193; or

j) a light chain variable domain comprising an amino acid sequence of SEQ ID NO: 211 and/or a heavy chain variable domain comprising an amino acid sequence of SEQ ID NO: 191, 192 or 193.

3. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:

(a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 194, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 174;

(b) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 195, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 175;

(c) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 202, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 181;

(d) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 205, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 184;

(e) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 206, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 184;

(f) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 205, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 185;

(g) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 206, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 185;

(h) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 205, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 186;

(i) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 206, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 186;

(j) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 207, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 187;

(k) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 208, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 187;

(l) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 207, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 188;

(m) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 208, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 188;

(n) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 207, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 189;

(o) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 208, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 189;

(p) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 207, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 190;

(q) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 208, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 190;

(r) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 209, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 191;

(s) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 210, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 191;

(t) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 211, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 191;

(u) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 209, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 192;

(v) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 210, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 192;

(w) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 211, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 192;

(x) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 209, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 193;

(y) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 210, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 193; or

(z) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 211, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 193.

4. The anti-Siglec-5 antibody of claim 1 , wherein the antibody is of the IgG class, the IgM class, or the IgA class.

5. The anti-Siglec-5 antibody of claim 4 , wherein the anti-Siglec-5 antibody has an IgG1, IgG2, IgG3, or IgG4 isotype.

6. The anti-Siglec-5 antibody of claim 5 , wherein the antibody binds an inhibitory Fc receptor.

7. The anti-Siglec-5 antibody of claim 6 , wherein the inhibitory Fc receptor is inhibitory Fc-gamma receptor IIB (FcγIIB).

8. The anti-Siglec-5 antibody of claim 7 , wherein:

(a) the anti-Siglec-5 antibody has a human or mouse IgG1 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: N297, D265, D270, L234, L235, G237, P238, L328, E233, H268, P271, A330, C226, C229, P331, S267, M252, S254, T256, A327, P329, K322, T394, E430, V263, V266, V273, and V305; wherein the amino acid substitution at the residue position N297 is N297A or N297Q; wherein the amino acid substitution at the residue position D265 is D265A; wherein the amino acid substitution at the residue position D270 is D270A; wherein the amino acid substitution at the residue position L234 is L234A or L234V or L234F; wherein the amino acid substitution at the residue position L235 is L235A or L235E; wherein the amino acid substitution at the residue position G237 is G237A or G237D; wherein the amino acid substitution at the residue position P238 is P238D or P238S or P238S; wherein the amino acid substitution at the residue position L328 is L328E or L328F; wherein the amino acid substitution at the residue position E233 is E233D or E233P; wherein the amino acid substitution at the residue position H268 is H268D; wherein the amino acid substitution at the residue position P271 is P271G; wherein the amino acid substitution at the residue position A330 is A330R or A330L; wherein the amino acid substitution at the residue position C226 is C226S; wherein the amino acid substitution at the residue position C229 is C229S; wherein the amino acid substitution at the residue position P331 is P331S; wherein the amino acid substitution at the residue position S267 is S267E; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; wherein the amino acid substitution at the residue position T256 is T256E; wherein the amino acid substitution at the residue position A327 is A327Q or A327G; wherein the amino acid substitution at the residue position P329 is P329A; wherein the amino acid substitution at the residue position K322 is K322A; wherein the amino acid substitution at the residue position T394 is T394D; wherein the amino acid substitution at the residue position E430 is E430G; wherein the amino acid substitution at the residue position V263 is V263L; wherein the amino acid substitution at the residue position V266 is V266L; wherein the amino acid substitution at the residue position V273 is V273C or V273E or V273F or V273L or V273M or V273S or V273Y; and wherein the amino acid substitution at the residue position V305 is V305K or V305W, wherein the numbering of the residues is according to EU numbering, or comprises an amino acid deletion in the Fc region at a position corresponding to glycine 236;

(b) the anti-Siglec-5 antibody has an IgG1 isotype and comprises an IgG2 isotype heavy chain constant domain 1 (CH1) and hinge region, optionally wherein the IgG2 isotype CH1 and hinge region comprises the amino acid sequence of ASTKGPSVFP LAPCSRSTSE STAALGCLVK DYFPEPVTVS WNSGALTSGVHTFPAVLQSS GLYSLSSVVT VPSSNFGTQT YTCNVDHKPS NTKVDKTVERKCCVECPPCP (SEQ ID NO: 218), and optionally wherein the antibody Fc region comprises a S267E amino acid substitution, a L328F amino acid substitution, or both, and/or a N297A or N297Q amino acid substitution, wherein the numbering of the residues is according to EU numbering;

(c) the anti-Siglec-5 antibody has an IgG2 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: P238, V234, G237, H268, V309, A330, P331, C214, C232, C233, S267, L328, M252, S254, T256, N297, C127, and E430; wherein the amino acid substitution at the residue position P238 is P238S; wherein the amino acid substitution at the residue position V234 is V234A; wherein the amino acid substitution at the residue position G237 is G237A; wherein the amino acid substitution at the residue position H268 is H268A or H268Q or H268E; wherein the amino acid substitution at the residue position V309 is V309L; wherein the amino acid substitution at the residue position A330 is A330S or A330L; wherein the amino acid substitution at the residue position P331 is P331S; wherein the amino acid substitution at the residue position C214 is C214S; wherein the amino acid substitution at the residue position C232 is C232S; wherein the amino acid substitution at the residue position C233 is C233S; wherein the amino acid substitution at the residue position S267 is S267E; wherein the amino acid substitution at the residue position L328 is L328F; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; wherein the amino acid substitution at the residue position T256 is T256E; wherein the amino acid substitution at the residue position N297 is N297A or N297Q; wherein the amino acid substitution at the residue position C127 is C127S; and wherein the amino acid substitution at the residue position E430 is E430G, wherein the numbering of the residues is according to EU numbering;

(d) the anti-Siglec-5 antibody has a human or mouse IgG4 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: L235, G237, S228, L236, S267, E318, L328, M252, S254, T256, E233, F234 or L234, S241, L248, T394, and N297; wherein the amino acid substitution at the residue position L235 is L235A or L235E; wherein the amino acid substitution at the residue position G237 is G237A; wherein the amino acid substitution at the residue position S228 is S228P; wherein the amino acid substitution at the residue position L236 is L236E; wherein the amino acid substitution at the residue position S267 is S267E; wherein the amino acid substitution at the residue position E318 is E318A; wherein the amino acid substitution at the residue position L328 is L328F; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; wherein the amino acid substitution at the residue position T256 is T256E; wherein the amino acid substitution at the residue position E233 is E233P; wherein the amino acid substitution at the residue position F234 is F234V or F234A or the amino acid substitution at residue position L234 is L234A; wherein the amino acid substitution at the residue position S241 is S241P; wherein the amino acid substitution at the residue position L248 is L248E; wherein the amino acid substitution at the residue position T394 is T394D; and wherein the amino acid substitution at the residue position N297 is N297A or N297Q, wherein the numbering of the residues is according to EU numbering; or

(e) the anti-Siglec-5 antibody has a hybrid IgG2/4 isotype, and optionally wherein the antibody comprises an amino acid sequence comprising amino acids 118 to 260 of human IgG2 and amino acids 261 to 447 of human IgG4 as set forth in SEQ ID NO: 218, wherein the numbering of the residues is according to EU numbering.

9. The anti-Siglec-5 antibody of claim 8 , wherein:

(a) the anti-Siglec-5 antibody has a human or mouse IgG1 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: N297, D270, D265, L234, L235, C226, C229, P238, E233, A327, P329, K322, P331, T394, A330, M252, S254, and T256; wherein the amino acid substitution at the residue position N297 is N297A or N297Q; wherein the amino acid substitution at the residue position D270 is D270A; wherein the amino acid substitution at the residue position D265 is D265A; wherein the amino acid substitution at the residue position L234 is L234A or L234F or L234V; wherein the amino acid substitution at the residue position L235 is L235A or L235E; wherein the amino acid substitution at the residue position C226 is C226S; wherein the amino acid substitution at the residue position C229 is C229S; wherein the amino acid substitution at the residue position P238 is P238S or P238A; wherein the amino acid substitution at the residue position E233 is E233P; wherein the amino acid substitution at the residue position A327 is A327Q or A327G; wherein the amino acid substitution at the residue position P239 is P329A; wherein the amino acid substitution at the residue position K322 is K322A; wherein the amino acid substitution at the residue position P331 is P331S; wherein the amino acid substitution at the residue position T394 is T394D; wherein the amino acid substitution at the residue position A330 is A330L; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; and wherein the amino acid substitution at the residue position T256 is T256E, wherein the numbering of the residues is according to EU numbering;

(b) the anti-Siglec-5 antibody has an IgG2 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: P238, V234, G237, H268, V309, N297, A330, P331, C232, C233, M252, S254, T256, C127, and E430; wherein the amino acid substitution at the residue position P238 is P238S; wherein the amino acid substitution at the residue position V234 is V234A; wherein the amino acid substitution at the residue position G237 is G237A; wherein the amino acid substitution at the residue position H268 is H268A or H268Q or H268E; wherein the amino acid substitution at the residue position V309 is V309L; wherein the amino acid substitution at the residue position N297 is N297A or N297Q; wherein the amino acid substitution at the residue position A330 is A330S; wherein the amino acid substitution at the residue position P331 is P331S; wherein the amino acid substitution at the residue position C232 is C232S; wherein the amino acid substitution at the residue position C233 is C233S; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; wherein the amino acid substitution at the residue position T256 is T256E; wherein the amino acid substitution at the residue position C127 is C127S; and wherein the amino acid substitution at the residue position E430 is E430G, wherein the numbering of the residues is according to EU numbering; or

(c) the anti-Siglec-5 antibody has an IgG4 isotype and comprises one or more amino acid substitutions in the Fc region at the residue position(s) selected from the group consisting of: E233, F234 or L234, L235, G237, E318, S228, L236, S241, L248, T394, M252, S254, T256, and N297; wherein the amino acid substitution at the residue position E233 is E233P; wherein the amino acid substitution at the residue position F234 is F234V or F234A or the amino acid substitution at residue position L234 is L234A; wherein the amino acid substitution at the residue position L235 is L235A; wherein the amino acid substitution at the residue position G237 is G237A; wherein the amino acid substitution at the residue position E318 is E318A; wherein the amino acid substitution at the residue position S228 is S228P; wherein the amino acid substitution at the residue position L236 is L236E; wherein the amino acid substitution at the residue position S241 is S241P; wherein the amino acid substitution at the residue position L248 is L248E; wherein the amino acid substitution at the residue position T394 is T394D; wherein the amino acid substitution at the residue position M252 is M252Y; wherein the amino acid substitution at the residue position S254 is S254T; wherein the amino acid substitution at the residue position T256 is T256E; and wherein the amino acid substitution at the residue position N297 is N297A or N297Q, wherein the numbering of the residues is according to EU numbering.

10. The anti-Siglec-5 antibody of claim 9 , wherein:

(a) the anti-Siglec-5 antibody has an IgG1 isotype and the Fc region comprises one or more additional amino acid substitutions selected from the group consisting of A330L, L234F, L235E, and P331S, wherein the numbering of the residues is according to EU numbering;

(b) the anti-Siglec-5 antibody has an IgG1, IgG2, or IgG4 isotype and the Fc region comprises one or more additional amino acid substitutions selected from the group consisting of M252Y, S254T, and T256E, wherein the numbering of the residues is according to EU numbering; or

(c) the anti-Siglec-5 antibody has an IgG4 isotype and the Fc region comprises a S228P amino acid substitution according to EU numbering.

11. The anti-Siglec-5 antibody of claim 1 , wherein the antibody has an IgG4 isotype.

12. The anti-Siglec-5 antibody of claim 11 , wherein the anti-Siglec-5 antibody comprises an S228P amino acid substitution at residue position 228, an F234A amino acid substitution at residue position 234, and an L235A amino acid substitution at residue position 235, wherein the numbering of the residue position is according to EU numbering.

13. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody is an antibody fragment that binds to an epitope comprising amino acid residues on human Siglec-5 protein.

14. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody is a murine antibody.

15. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody is a humanized antibody, a bispecific antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody.

16. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody is a conjugated antibody.

17. The anti-Siglec-5 antibody of claim 16 , wherein the anti-Siglec-5 antibody is conjugated to a detectable marker, a toxin, or a therapeutic agent.

18. The anti-Siglec-5 antibody of claim 17 , wherein the anti-Siglec-5 antibody is conjugated to a toxin selected from the group consisting of ricin, doxorubicin, daunorubicin, a maytansinoid, taxol, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, modeccin A chain, alpha-sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, inhibitor derived from Saponaria officinalis , glucocorticoid, auristatin, auromycin, yttrium, bismuth, combrestatin, duocarmycins, dolastatin, cc1065, and a cisplatin.

19. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody has dissociation constant (K D ) for human Siglec-5 and mammalian Siglec-5 that ranges from 0.42 nM to 79 nM, wherein the K D is determined at a temperature of 25° C.

20. The anti-Siglec-5 antibody of claim 1 , wherein the anti-Siglec-5 antibody has dissociation constant (K D ) for human Siglec-5 that ranges from 79 nM to 61 nM, from 15 nM to 5.3 nM, or from 1.7 nM to 0.42 nM, wherein the K D is determined at a temperature of 25° C.

21. A pharmaceutical composition comprising the anti-Siglec-5 antibody of claim 1 , and a pharmaceutically acceptable carrier.

22. A method of inducing or promoting the survival, maturation, functionality, migration, or proliferation of one or more immune cells in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of the anti-Siglec-5 antibody of claim 1 .

23. A method of decreasing cellular levels of Siglec-5 on one or more cells in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an isolated anti-Siglec-5 antibody of claim 1 .

24. A method of relieving one or more immunosuppressed neutrophils in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of the anti-Siglec-5 antibody of claim 1 .

25. A method of increasing phagocytosis activity in macrophages in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of the anti-Siglec-5 antibody of claim 1 .

26. A method of inducing reactive oxygen species (ROS) production in one or more neutrophils in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an isolated monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain comprises an HVR-L1, an HVR-L2, and an HVR-L3, and the heavy chain variable domain comprises an HVR-H1, an HVR-H2, and an HVR-H3, wherein:

a) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 127, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 153, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 20, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 39, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 70;

b) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 114, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 127, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 153, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 20, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 49, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 70;

c) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 104, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 128, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 154, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 21, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 40, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 71; or

d) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 115, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 128, the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 154, the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 21, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 50, and the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 71.

27. A method of inducing neutrophil extracellular trap (NET) formation in one or more neutrophils in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an isolated monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain comprises an HVR-L1, an HVR-L2, and an HVR-L3, and the heavy chain variable domain comprises an HVR-H1, an HVR-H2, and an HVR-H3, wherein:

28. A method of inducing neutrophil activation in one or more neutrophils in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an isolated monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain comprises an HVR-L1, an HVR-L2, and an HVR-L3, and the heavy chain variable domain comprises an HVR-H1, an HVR-H2, and an HVR-H3, wherein:

29. An isolated nucleic acid comprising a nucleic acid sequence encoding the anti-Siglec-5 antibody of claim 1 .

30. A vector comprising the nucleic acid of claim 29 .

31. An isolated host cell comprising the vector of claim 30 .

32. A method of producing an anti-Siglec-5 antibody, comprising culturing the host cell of claim 31 so that the anti-Siglec-5 antibody is produced.

33. The method of claim 32 , further comprising recovering the anti-Siglec-5 antibody produced by the host cell.

34. An isolated anti-Siglec-5 antibody produced by the method of claim 32 .

Assignments (2)

SECURITY INTEREST Recorded Nov 14, 2024

From: ALECTOR, INC.; ALECTOR LLC

To: HERCULES CAPITAL, INC., AS AGENT

Reel/Frame 069386/0141 →

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