IP Library › Granted Patent US 12,331,112
Granted Patent B2
US 12,331,112 · App. 17/821,010 · 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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Quick Facts
Patent No.
US 12,331,112
App. No.
17/821,010
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 (29)

1. An isolated nucleic acid comprising a nucleic acid sequence encoding 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 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 MS4A4A, 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 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. A vector comprising the nucleic acid of claim 6 .

8. The vector of claim 2 , wherein said vector is a plasmid, a phage vector, a viral vector, a bacterial vector, an episomal mammalian vector, a non-episomal mammalian vector, or a recombinant expression vector.

9. The vector of claim 7 , wherein said vector is a plasmid, a phage vector, a viral vector, a bacterial vector, an episomal mammalian vector, a non-episomal mammalian vector, or a recombinant expression vector.

10. An isolated host cell comprising the vector of claim 7 .

11. The isolated host cell of claim 10 , wherein the host cell comprises a first vector comprising the nucleic acid that encodes the amino acid sequence comprising the heavy chain variable region of the antibody and a second vector comprising the nucleic acid that encodes the amino acid sequence comprising the light chain variable region of the antibody.

12. The host cell of claim 3 , wherein said host cell is a prokaryotic cell, a fungi cell, a yeast cell, a plant cell, an insect cell, or a mammalian cell.

13. The host cell of claim 12 , wherein the mammalian cell is selected from the group consisting of: Chinese Hamster Ovary cell, a lymphoid cell, a monkey kidney CV1 line transformed by SV40 cell, a human embryonic kidney line 293 cell, a baby hamster kidney cell, a mouse sertoli cell, a monkey kidney cell, an African green monkey kidney cell, a human cervical carcinoma cell, a canine kidney cell, a human lung cell, a human liver cell, a mouse mammary tumor cell, a TRI cell, a MRC 5 cell, and a FS4 cell.

14. The host cell of claim 10 , wherein said host cell is a prokaryotic cell, a fungi cell, a yeast cell, a plant cell, an insect cell, or a mammalian cell.

15. The host cell of claim 14 , wherein the mammalian cell is selected from the group consisting of: Chinese Hamster Ovary cell, a lymphoid cell, a monkey kidney CV1 line transformed by SV40 cell, a human embryonic kidney line 293 cell, a baby hamster kidney cell, a mouse sertoli cell, a monkey kidney cell, an African green monkey kidney cell, a human cervical carcinoma cell, a canine kidney cell, a human lung cell, a human liver cell, a mouse mammary tumor cell, a TRI cell, a MRC 5 cell, and a FS4 cell.

16. A method of producing an antibody that binds to human MS4A4A, comprising culturing the cell of claim 10 so that the antibody is produced.

17. The method of claim 16 , further comprising recovering the antibody produced by the cell.

18. The nucleic acid 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.

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

20. The nucleic acid of claim 19 , wherein the antibody is of the IgG class and has an IgG1, IgG2, or IgG4 isotype.

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

22. The nucleic acid of claim 21 , wherein the fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.

23. The nucleic acid of claim 1 , 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 of SEQ ID NOs: 15, 32, 50, 69, 82, and 96, respectively.

24. The nucleic acid of claim 1 , 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 of SEQ ID NOs: 18, 35, 53, 72, 77, and 99, respectively.

25. The nucleic acid of claim 1 , 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 of SEQ ID NOs: 143, 155, 169, 184, 198, and 211, respectively.

26. The nucleic acid of claim 6 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences of SEQ ID NOs: 115 and 134, respectively.

27. The nucleic acid of claim 6 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences of SEQ ID NOs: 118 and 137, respectively.

28. The nucleic acid of claim 6 , wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences of SEQ ID NOs: 226 and 241, respectively.

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 20230142579A1 · May 11, 2023
References Cited (108)
US 9969799B2 · Wang et al. · 2018 [cited by applicant]
US 11472874B2 · Kong et al. · 2022 [cited by applicant]
US 11667699B2 · Sun et al. · 2023 [cited by applicant]
US 20090011409A1 · Sharma et al. · 2009 [cited by applicant]
US 20160376359A1 · Wang et al. · 2016 [cited by applicant]
US 20170355756A1 · Julien et al. · 2017 [cited by applicant]
US 20210040200A1 · Kong et al. · 2021 [cited by applicant]
US 20210079074A1 · Kong et al. · 2021 [cited by applicant]
US 20210122817A1 · Kong et al. · 2021 [cited by applicant]
US 20220380455A1 · Kong et al. · 2022 [cited by applicant]
US 20230126400A1 · Kong et al. · 2023 [cited by applicant]
CN 101001879A · 2007 [cited by applicant]
CN 101998992A · 2011 [cited by applicant]
CN 105759057A · 2016 [cited by applicant]
CN 105969901A · 2016 [cited by applicant]
WO WO02062946A2 · 2002 [cited by applicant]
WO WO2003035689A1 · 2003 [cited by applicant]
WO WO2005040796A1 · 2005 [cited by applicant]
WO WO2005123779A2 · 2005 [cited by applicant]
WO WO2008068048A2 · 2008 [cited by applicant]
WO WO2011147851A1 · 2011 [cited by applicant]
WO WO2017143036A1 · 2017 [cited by applicant]
WO WO2019152706A1 · 2019 [cited by applicant]
WO WO2019152715A1 · 2019 [cited by applicant]
WO WO2020160468A1 · 2020 [cited by applicant]
WO WO2021022083A2 · 2021 [cited by applicant]
WO WO2021081101A1 · 2021 [cited by applicant]
WO WO2024086796A1 · 2024 [cited by applicant]
Al-Shawi, R., et al., “Neurotoxic and Neurotrophic Roles of ProNGF and the Receptor Sortilin in the Adult and Ageing Nervous System,” [cited by applicant]
Allen, M., et al., “Novel late-onset Alzheimer disease loci variants associate with brain gene expression,” [cited by applicant]
Antúnez, C., et al., “The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease,” [cited by applicant]
Arnett, M.J., et al., “Pro-NGF, Sortilin, and p75 [cited by applicant]
Barber, R.C., “The Genetics of Alzheimer's Disease,” [cited by applicant]
Beattie, M.S., et al., “ProNGF Induces p75-mediated Death of Oligodendrocytes Following Spinal Cord Injury,” [cited by applicant]
Bubien, J.K., et al., “Transfection of the CD20 Cell Surface Molecule Into Ectopic Cell Types Generates a Ca [cited by applicant]
Cruse, G., et al., “The CD20 Homologue MS4A4 Directs Trafficking of KIT Toward Clathrin-independent Endocytosis Pathways and Thus Regulates Receptor Signaling and Recycling,” [cited by applicant]
Deming, Y., et al., “The MS4A gene cluster is a key regulator of soluble TREM2 and Alzheimer disease risk,” [cited by applicant]
Denardo, D.G., et al., “Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy,” [cited by applicant]
Drake, A. W., and Klakamp, S.L., “A Rigorous Multiple Independent Binding Site Model for Determining Cell-based Equilibrium Dissociation Constants,” [cited by applicant]
Efthymiou, A.G., and Goate, A.M., “Late Onset Alzheimer's Disease Genetics Implicates Microglial Pathways in Disease Risk,” [cited by applicant]
Elias-Sonnenschein, L.S., et al., “Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort,” [cited by applicant]
Engle, S.J., et al., “Best Practices For Translational Disease Modeling Using Human iPSC-derived Neurons,” [cited by applicant]
Fahnestock, M., et al., “The Precursor Pro-nerve Growth Factor is the Predominant Form of Nerve Growth Factor in Brain and is Increased in Alzheimer's Disease,” [cited by applicant]
Fan, Y.J., et al., “Differential Effects of Pro-BDNF on Sensory Neurons After Sciatic Nerve Transection in Neonatal Rats,” [cited by applicant]
Greer, P.L., et al., “A Family of Non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction,” [cited by applicant]
Harrington, A.W., et al., “Secreted ProNGF is a Pathophysiological Death-inducing Ligand After Adult CNS Injury,” [cited by applicant]
Hollingworth, P., et al., “Common Variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP Are Associated With Alzheimer's Disease,” [cited by applicant]
Idusogie, E.E., et al., “Mapping of the C1q Binding Site on Rituxan, A Chimeric Antibody with a Human IgG1 Fc,” [cited by applicant]
Ishibashi, K., et al., “Identification of a New Multigene Four-transmembrane Family (MS4A) Related to CD20, HTm4 and β Subunit of the High-affinity IgE Receptor,” [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2019/016156, European Patent Office, Netherlands, mailed on Apr. 23, 2019, 13 pages. [cited by applicant]
Jansen, P., et al., “Roles for the Pro-neurotrophin Receptor Sortilin in Neuronal Development, Aging and Brain Injury,” [cited by applicant]
Karch, C.M., et al., “Expression of novel Alzheimer's disease risk genes in control and Alzheimer's disease brains,” [cited by applicant]
Karch, C.M., et al., “Alzheimer's disease risk genes and mechanisms of disease pathogenesis,” [cited by applicant]
Kay, B.K., et al., “The Importance of Being Proline: the Interaction of Proline-rich Motifs in Signaling Proteins With Their Cognate Domains,” [cited by applicant]
Koslowski, M., et al., “MS4A12 is a Colon-selective Store-operated Calcium Channel Promoting Malignant Cell Processes,” [cited by applicant]
Kuek, L.E., et al., “The MS4A family: counting past 1, 2 and 3,” [cited by applicant]
Lambert, J.C., et al., “Meta-analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer's Disease,” [cited by applicant]
Liang, Y., and Tedder, T.F., “Identification of a CD20-, FcεRIβ-, and HTm4-related Gene Family: Sixteen New MS4A Family Members Expressed in Human and Mouse,” [cited by applicant]
Liang, C.C., et al., “In Vitro Scratch Assay: a Convenient and Inexpensive Method for Analysis of Cell Migration in Vitro,” [cited by applicant]
Ma, J., et al., “MS4A6A genotypes are associated with the atrophy rates of Alzheimer's disease related brain structures,” [cited by applicant]
Murthy, M.N., et al., “Increased Brain Expression of GPNMB Is Associated with Genome Wide Significant Risk for Parkinson's Disease on Chromosome 7p15.3,” [cited by applicant]
Naj, A.C., et al., “Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 Are Associated With Late-onset Alzheimer's Disease,” [cited by applicant]
Nakamura, K., et al., “Intracellular Sortilin Expression Pattern Regulates ProNGF-induced Naturally Occurring Cell Death During Development,” [cited by applicant]
Nykjaer, A., et al., “Sortilin is Essential for ProNGF-induced Neuronal Cell Death,” [cited by applicant]
Nykjaer, A., et al., “P75 [cited by applicant]
Peng, X., et al., “Preclinical Evaluation of 3D185, a Novel Potent Inhibitor of FGFR1/2/3 and CSF-1R, in FGFR-Dependent and Macrophage-Dominant Cancer models,” [cited by applicant]
Piccio, L., et al., “Cerebrospinal Fluid Soluble TREM2 is Higher in Alzheimer Disease and Associated With Mutation Status,” [cited by applicant]
Pocock, J.M., et al., “Modelling Microglial Function With Induced Pluripotent Stem Cells: An Update,” [cited by applicant]
Provenzano, M.J., et al., “P75NTR and Sortilin Increase After Facial Nerve Injury,” [cited by applicant]
Salimi, A., et al., “Comparison Of Different Protocols For Neural Differentiation Of Human Induced Pluripotent Stem Cells,” [cited by applicant]
Sanyal, R., et al., “MS4A4A: a novel cell surface marker for M2 macrophages and plasma cells,” [cited by applicant]
Shang, L., et al., “Selective Antibody Intervention of Toll-like Receptor 4 Activation through Fc γ Receptor Tethering,” [cited by applicant]
Tcw, J., et al., “An Efficient Platform For Astrocyte Differentiation From Human Induced Pluripotent Stem Cells,” [cited by applicant]
Teng, H.K., et al., “ProBDNF Induces Neuronal Apoptosis via Activation of a Receptor Complex of P75 [cited by applicant]
Thornton, P., et al., “TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant,” [cited by applicant]
Tomay, F., “Regulation and function of the tetraspanin-like molecule MS4A4A in alternatively activated and tumor-associated macrophages,” XP055578452, Retrieved from the Internet: https://air.unimi.it/retrieve/handle/24… [cited by applicant]
Volosin, M., et al., “Interaction of Survival and Death Signaling in Basal Forebrain Neurons: Roles of Neurotrophins and Proneurotrophins,” [cited by applicant]
Volosin, M., et al., “Induction of Proneurotrophins and Activation of P75 [cited by applicant]
Wei, Y., et al., “Enhanced Protein Expressions of Sortilin and P75 [cited by applicant]
Yano, H., et al., “Proneurotrophin-3 Is a Neuronal Apoptotic Ligand: Evidence for Retrograde-Directed Cell Killing,” [cited by applicant]
Chen, C., et al., “Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations,” EMBO Journal 14(12):2784-2794, Oxford University Press, Un… [cited by applicant]
International Search Report and Written Opinion mailed Jan. 28, 2021, in Application No. PCT/US2020/044335, EPO, Netherlands, 15 pages. [cited by applicant]
Kussie, P.H., et al., “A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity,” Journal of Immunology 152(1):146-152, American Association of Immunology, United States (1994). [cited by applicant]
Office Action mailed Oct. 18, 2021 in U.S. Appl. No. 16/943,123, inventor Sun, J., et al., filing date Jul. 30, 2020, 15 pages. [cited by applicant]
Reitz, C., “Toward Precision medicine in Alzheimer's Disease,” Ann. Transl. Med 4(6):107, 7 pages, AME Publishing Corp, United States (2016). [cited by applicant]
Stanford Health Now, “Alzheimer's Prevention, Treatment and Research—A Q&A with Dr. Frank Longo,” retrieved from: stanfordhealthcare.org/Stanford-health-now/2016/alzheimers-prevention-treatment-research-qa-longo.html, a… [cited by applicant]
Proitsi, P., et al., “Alzheimer's disease susceptibility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood,” Neurobiol Aging 35(2):279-290, Elseiver, Netherlands (2013). [cited by applicant]
International Search Report and Written Opinion mailed Jan. 28, 2021, in Application No. PCT/US2019/016141, KIPO, Korea, 11 pages. [cited by applicant]
Puri, M., et al., “The Evaluation of MS4A4A and MS4A8B Expression in Hematopoietic Cells,” retrieved from: https://prism.ucalgary.ca/bitstream/handle/11023/1791/ucalgary2014purmandip.pdf;jsessionid=cda23b615634fb7f5836e… [cited by applicant]
Koenig, P., et al., “Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding,” [cited by applicant]
Office Action mailed Jun. 16, 2022, in U.S. Appl. No. 16/943,123, Sun, J., et al., filed Jul. 30, 2020, 7 pages. [cited by applicant]
Office Action mailed Feb. 28, 2022, in U.S. Appl. No. 16/965,676, Kong, P., et al., filed Jul. 29, 2020, 16 pages. [cited by applicant]
Office Action mailed Oct. 3, 2022, in U.S. Appl. No. 16/943,123, Sun, J., et al., filed Jul. 30, 2020, 3 pages. [cited by applicant]
Sekine, S. “The Current State and the Issues of Antibody Drugs,” [cited by applicant]
Edwards, B.M., et al., “The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS,” J Mol Biol 334(1):103-18, Elsevier, Netherlands (Nov. … [cited by applicant]
NCBI, “Membrane-spanning 4-domains subfamily A member 4A isoform 1 [ [cited by applicant]
Hu, X., et al., “Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment,” Transl Psychiatry 1:e54, 9 pages, Macmillian Publishers Ltd.… [cited by applicant]
Lacher, S.E., et al., “A Hypermorphic Antioxidant Response Element is Associated With Increased MS4A6A Expression and Alzheimer's Disease,” Redox Biology 14:686-693, Elsevier, B.V., Netherlands (Oct. 2017). [cited by applicant]
Ma, J., et al., “MS4A Cluster in Alzheimer's Disease,” Molecular Neurobiology 51(3):1240-1248, Humana Press, United States (2015). [cited by applicant]
Maximov, A., et al., “Monitoring Synaptic Transmission in Primary Neuronal Cultures Using Local Extracellular Stimulation,” Journal of Neuroscience Methods 161(1):75-87, Elsevier, Netherlands (Mar. 2007). [cited by applicant]
He Li, W., “Research progress in MS4A gene family and tumor,” Tumor 36:345-350, China Academic Journal Electronic Publishing House, China (Mar. 2016). [cited by applicant]
He Li, W., “Research progress on MS4A gene family and clinically relevant diseases,” Chin J Clin Lab Sci 34(3):202-204, Chinese Medical Journals Publishing House, China (Mar. 2016). [cited by applicant]
Morris, G.E., et al., “Epitope Mapping of Protein Antigens by Competition ELISA,” The Protein Protocols Handbook, pp. 595-600, Humana Press, United States (1996). [cited by applicant]
Rudikoff, S., et al., “Single amino acid substitution altering antigen-binding specificity,” Proc Natl Acad Sci USA 79(6):1979-1983, National Academy of Sciences, United States (Mar. 1982). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2023/077418, European Patent Office, Netherlands, mailed Feb. 12, 2024, 13 pages. [cited by applicant]
You, S-F., et al., “MS4A4A modifies the risk of Alzheimer disease by regulating lipid metabolism and immune response in a unique microglia state,” MedRxiv 10.1101/2023.02.06.23285545, accessed at https://www.medrixiv.or… [cited by applicant]
Dondelinger, M., et al., “Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition,” Front Immunol 9:2278, pp. 1-15, Frontiers Media SA., Switzerland (Oct. 201… [cited by applicant]
Sela-Culang, I., et al., “The structural basis of antibody-antigen recognition,” Front Immunol 4:302, pp. 1-13, Frontiers Media SA., Switzerland (Oct. 2013). [cited by applicant]