# US 11,999,779 B2 · Anti-complement factor C1q Fab fragments and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,999,779 B2
- Document ID: US11999779B2
- Status: Granted
- Kind: B2
- Application number: 16/911,954
- Filed: 2020-06-25
- Published: 2020-10-08
- Granted: 2024-06-04
- Earliest claimed: 2015-11-24
- Assignees: Annexon, Inc.
- Applicants: Annexon, Inc.
- Inventors: Ted Yednock; Sethu Sankaranarayanan; Michael Leviten; Arnon Rosenthal
- Web page: https://patentgrep.com/patent/US11999779B2

## CPC

- C07K 16/18: against material from animals or humans
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/06: Antianaemics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/04: Artificial tears; Irrigation solutions
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9}
- G01N 33/6857: {Antibody fragments}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/4716: Complement proteins, e.g. anaphylatoxin, C3a, C5a
- G01N 2800/50: Determining the risk of developing a disease
- G01N 2800/7095: Inflammation
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure relates generally to anti-C1q antibody Fab fragments and methods of using the same.

## Claims

### Claim 1

A method of inhibiting synapse loss comprising administering to a patient suffering from adverse synapse loss an antibody Fab fragment that binds to C1q, wherein the antibody Fab fragment comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO:1 and the light chain comprises SEQ ID NO:2.

### Claim 2 (depends on 1)

The method of claim 1, wherein the patient has suffered synapse loss as a result of a neurodegenerative disorder, central nervous system disorder, or a peripheral nervous system disorder.

### Claim 3 (depends on 2)

The method of claim 2, wherein the neurodegenerative disorder is Alzheimer's disease.

### Claim 4 (depends on 1)

The method of claim 1, further comprising administration of neural progenitors, or a neurogenesis enhancer.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody Fab fragment binds to C1q and inhibits complement activation.

### Claim 6

A method of treating a disease associated with C1q mediated activation of the classical complement pathway in an individual in need of such treatment, the method comprising administering an antibody Fab fragment that binds to C1q, wherein the antibody Fab fragment comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO:1 and the light chain comprises SEQ ID NO:2.

### Claim 7 (depends on 6)

The method of claim 6, wherein the disease associated with C1q mediated activation of the classical complement pathway is a neurodegenerative disorder.

### Claim 8 (depends on 7)

The method of claim 7, wherein the neurodegenerative disorder is associated with loss of synapses or loss nerve connections.

### Claim 9 (depends on 7)

The method of claim 7, wherein the neurodegenerative disorder is associated with synapse loss that is dependent on the complement receptor 3(CR3)/C3 or complement receptor CR1.

### Claim 10 (depends on 7)

The method of claim 7, wherein the neurodegenerative disorder is associated with pathological activity-dependent synaptic pruning.

### Claim 11 (depends on 7)

The method of claim 7, wherein the neurodegenerative disorder is associated with synapse phagocytosis by microglia.

### Claim 12 (depends on 7)

The method of claim 7, wherein the neurodegenerative disorder is selected from Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, Guillain-Barre' syndrome (GBS), Myasthenia Gravis, Bullous Pemphigoid, spinal muscular atrophy, Down syndrome, Parkinson's disease, or Huntington's disease.

### Claim 13 (depends on 6)

The method of claim 6, wherein the disease associated with C1q mediated activation of the classical complement pathway is an inflammatory disease, autoimmune disease, complement-associated eye disease or metabolic disorder.

### Claim 14 (depends on 13)

The method of claim 13, wherein the inflammatory disease, autoimmune disease, complement-associated eye disease or metabolic disorder is selected from diabetes, obesity, rheumatoid arthritis (RA), acute respiratory distress syndrome (ARDS), remote tissue injury after ischemia and reperfusion, complement activation during cardiopulmonary bypass surgery, dermatomyositis, pemphigus, lupus nephritis and resultant glomerulonephritis and vasculitis, cardiopulmonary bypass, cardioplegia-induced coronary endothelial dysfunction, type II membranoproliferative glomerulonephritis, IgA nephropathy, acute renal failure, cryoglobulinemia, antiphospholipid syndrome, Chronic open-angle glaucoma, acute closed angle glaucoma, macular degenerative diseases, age-related macular degeneration (AMD), geographic atrophy, choroidal neovascularization (CNV), uveitis, diabetic retinopathy, ischemia-related retinopathy, endophthalmitis, intraocular neovascular disease, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, histoplasmosis of the eye, Neuromyelitis Optica (NMO), Central Retinal Vein Occlusion (CRVO), corneal neovascularization, retinal neovascularization, Leber's hereditary optic neuropathy, optic neuritis, Behcet's retinopathy, ischemic optic neuropathy, retinal vasculitis, ANCA vasculitis, Purtscher retinopathy, Sjogren's dry eye disease, dry AMD, sarcoidosis, temporal arteritis, polyarteritis nodosa, multiple sclerosis, allo-transplantation, hyperacute rejection, hemodialysis, chronic occlusive pulmonary distress syndrome (COPD), asthma, aspiration pneumonia, multiple sclerosis, Guillain-Barre syndrome, Myasthenia Gravis, Bullous Pemphigoid, or myositis.

### Claim 15 (depends on 6)

The method of claim 6, wherein the disease associated with C1q mediated activation of the classical complement pathway is an autoimmune disease selected from myasthenia gravis, Diabetes mellitus type 1, Hashimoto's thyroiditis, Addison's disease, Coeliac disease, Crohn's disease, pernicious anaemia, Pemphigus vulgaris, vitiligo, autoimmune hemolytic anemias, paraneoplastic syndromes, a vasculitis disease, hypocomplementemic urticarial vasculitis (HUV), polymyalgia rheumatica, temporal arteritis, Wegener's granulomatosis, multiple sclerosis, Guillain-Barre syndrome, Myasthenia Gravis, Bullous Pemphigoid, or myositis.

### Claim 16 (depends on 1)

The method of claim 1, wherein the antibody Fab fragment has a dissociation constant (KD) for mouse C1q in the range of from 1 pM to 200 pM.

### Claim 17 (depends on 1)

The method of claim 1, wherein the antibody Fab fragment is humanized.

### Claim 18 (depends on 6)

The method of claim 6, wherein the antibody Fab fragment has a dissociation constant (KD) for mouse C1q in the range of from 1 pM to 200 pM.

### Claim 19 (depends on 6)

The method of claim 6, wherein the antibody Fab fragment is humanized.