# US 12,110,321 B2 · Single domain antibodies for complement regulation

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- Number: US 12,110,321 B2
- Document ID: US12110321B2
- Status: Granted
- Kind: B2
- Application number: 17/251,023
- Filed: 2019-06-11
- Published: 2021-08-19
- Granted: 2024-10-08
- Earliest claimed: 2018-06-11
- Assignees: Aarhus Universitet
- Applicants: Aarhus Universitet
- Inventors: Nick Stub Laursen; Dennis Vestergaard Pedersen; Gregers Rom Andersen; Steffen Thiel; Alessandra Zarantonello; Rasmus Kjeldsen Jensen; Henrik Pedersen
- Web page: https://patentgrep.com/patent/US12110321B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Single domain antibodies are provided, which are capable of specifically binding to an epitope of a human complement factor selected from the group consisting of C1q, C3, C4 and/or the proteolytic derivatives C3b and C4b. Further the use of the antibodies are provided for methods in modulating the activity of the complement system as well 5 as methods of treating disorders associated with complement activation.

## Claims

### Claim 1

A single domain antibody capable of specifically binding to an epitope of a human and/or mouse C1q complement factor, wherein the single domain antibody comprises a complementarity determining region-1 (CDR1), a complementarity determining region-2 (CDR2), and a complementarity determining region-3 (CDR3); wherein:
(a) the CDR1 comprises the amino acid sequence of SEQ ID NO: 10, the CDR2 comprises the amino acid sequence of SEQ ID NO: 11, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 12;
(b) the CDR1 comprises the amino acid sequence of SEQ ID NO: 14, the CDR2 comprises the amino acid sequence of SEQ ID NO: 15, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 16;
(c) the CDR1 comprises the amino acid sequence of SEQ ID NO: 18, the CDR2 comprises the amino acid sequence of SEQ ID NO: 19, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 20;
(d) the CDR1 comprises the amino acid sequence of SEQ ID NO: 22, the CDR2 comprises the amino acid sequence of SEQ ID NO: 23, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 24;
(e) the CDR1 comprises the amino acid sequence of SEQ ID NO: 26, the CDR2 comprises the amino acid sequence of SEQ ID NO: 27, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 28;
(f) the CDR1 comprises the amino acid sequence of SEQ ID NO: 30, the CDR2 comprises the amino acid sequence of SEQ ID NO: 31, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 32;
(g) the CDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CDR2 comprises the amino acid sequence of SEQ ID NO: 35, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 36; or
(h) the CDR1 comprises the amino acid sequence of SEQ ID NO: 38, the CDR2 comprises the amino acid sequence of SEQ ID NO: 39, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 40.

### Claim 2 (depends on 1)

The single domain antibody according to claim 1, wherein said antibody is fused to another entity or moiety.

### Claim 3 (depends on 2)

The single domain antibody according to claim 2, wherein said another entity or moiety binds a cancer-specific marker, a pathogenic marker, a tissue-specific marker or an organ-specific marker.

### Claim 4 (depends on 1)

The single domain antibody according to claim 1, wherein the said antibody binds said complement factor with an affinity corresponding to a KD of about 10−6 M or less.

### Claim 5 (depends on 1)

A composition that comprises the single domain antibody of claim 1.

### Claim 6 (depends on 5)

The composition of claim 5, further comprising an additional entity or moiety.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the single domain antibody and the additional entity or moiety are fused by a linker.

### Claim 8 (depends on 6)

The composition of claim 6, wherein the additional entity or moiety is albumin.

### Claim 9 (depends on 7)

The composition of claim 7, wherein the additional entity or moiety is a binding moiety that binds to a cancer-specific marker, a pathogenic marker, a tissue-specific marker or an organ-specific marker.

### Claim 10

A single domain antibody capable of specifically binding to an epitope of a human and/or mouse C1q complement factor,
wherein the single domain antibody comprises a complementarity determining region-1 (CDR1), a complementarity determining region-2 (CDR2), and a complementarity determining region-3 (CDR3),
wherein the CDR1 comprises the amino acid sequence of SEQ ID NO: 18 or a functional variant thereof, wherein the functional variant comprises a single amino acid substitution,
wherein the CDR2 comprises the amino acid sequence of SEQ ID NO: 19 or a functional variant thereof, wherein the functional variant comprises a single amino acid substitution, and
wherein the CDR3 comprises the amino acid sequence of SEQ ID NO: 20.

### Claim 11 (depends on 10)

The single domain antibody according to claim 10, wherein said antibody is fused to another entity or moiety.

### Claim 12 (depends on 11)

The single domain antibody according to claim 11, wherein said another entity or moiety binds a cancer-specific marker, a pathogenic marker, a tissue-specific marker or an organ-specific marker.

### Claim 13 (depends on 10)

The single domain antibody according to claim 10, wherein the said antibody binds said complement factor with an affinity corresponding to a KD of about 10−6 M or less.

### Claim 14 (depends on 10)

A composition that comprises the single domain antibody of claim 10.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the single domain antibody is fused to an additional entity or moiety.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the single domain antibody and the additional entity or moiety are fused by a linker.

### Claim 17 (depends on 15)

The composition of claim 15, wherein the additional entity or moiety is albumin.

### Claim 18 (depends on 15)

The composition of claim 15, wherein the additional entity or moiety is a binding moiety that binds to a cancer-specific marker, a pathogenic marker, a tissue-specific marker or an organ-specific marker.