# US 11,439,706 B2 · Polynucleotides encoding a humanized anti-CD40 antibody

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- Number: US 11,439,706 B2
- Document ID: US11439706B2
- Status: Granted
- Kind: B2
- Application number: 16/994,249
- Filed: 2020-08-14
- Published: 2020-12-10
- Granted: 2022-09-13
- Earliest claimed: 2015-09-04
- Assignees: Primatope Therapeutics Inc.
- Applicants: Primatope Therapeutics Inc.
- Inventors: Bo Yu; Rijian Wang; Keith Reimann
- Web page: https://patentgrep.com/patent/US11439706B2

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/18: against material from animals or humans
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- 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
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure relates to anti-CD40 antibodies, such as humanized anti-CD40 antibodies, that may be used in various therapeutic, prophylactic and diagnostic methods. The antibodies generally block the ability of CD40 to bind CD154 and do so without activating the cell expressing CD40 (e.g., a B cell). The present antibodies or fragments thereof may be used to reduce complications associated with organ or tissue transplantation.

## Claims

### Claim 1

A polynucleotide encoding a humanized anti-CD40 antibody or antigen-binding fragment thereof comprising a heavy chain variable region comprising an amino acid sequence with at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 19, 20, 21, 24, 25, and 26 and a light chain variable region comprising an amino acid sequence with at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 22, 23, 27, 28, and 29, wherein the heavy chain variable region comprises a CDR1, CDR2, and CDR3 with the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively, and wherein the light chain variable region comprises a CDR1, CDR2, and CDR3 with the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively.

### Claim 2 (depends on 1)

The polynucleotide of claim 1, wherein the amino acid sequence of the heavy chain variable region has at least 90%, 95%, or 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 19, 20, 21, 24, 25, and 26, and the amino acid sequence of the light chain variable region has at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 22, 23, 27, 28, and 29.

### Claim 3 (depends on 2)

The polynucleotide of claim 2, wherein the amino acid sequence of the heavy chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19, 20, 21, 24, 25, and 26, and the amino acid sequence of the light chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NOs: 22, 23, 27, 28 and 29, wherein the antibody or antigen-binding fragment thereof does not comprise the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 21 and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23.

### Claim 4 (depends on 1)

The polynucleotide of claim 1, wherein:
a) the dissociation constant (KD) of the antibody or antigen-binding fragment thereof is less than about 1×10−9 M;
b) the antibody or antigen-binding fragment thereof is selected from the group consisting of: (a) a whole immunoglobulin molecule; (b) an scFv; (c) a Fab fragment; (d) an F(ab′)2; and (e) a disulfide linked Fv;
c) the antibody or antigen-binding fragment thereof comprises at least one constant domain selected from the group consisting of: a) an IgG constant domain; and (b) an IgA constant domain;
d) the antibody or antigen-binding fragment thereof comprises at least one human constant domain;
e) the antibody or antigen-binding fragment thereof binds to CD40 extracellular domain;
f) the CD40 is human or rhesus CD40;
g) the antibody or antigen-binding fragment thereof blocks B lymphocyte activation by CD154-expressing Jurkat cells in vitro; and/or
h) the antibody or antigen-binding fragment thereof inhibits B lymphocyte CD23, CD80, or CD86 expression.

### Claim 5 (depends on 1)

A vector comprising the polynucleotide of claim 1.

### Claim 6 (depends on 5)

A cell comprising the vector of claim 5.

### Claim 7 (depends on 6)

The cell of claim 6, wherein the cell is a eukaryotic cell or a prokaryotic cell.

### Claim 8 (depends on 7)

The cell of claim 7, wherein the eukaryotic cell is a mammalian cell.

### Claim 9 (depends on 1)

A composition comprising the polynucleotide of claim 1, a vector comprising the polynucleotide, or a cell comprising the vector, and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 1)

A method of producing an antibody or antigen-binding fragment thereof comprising the steps of:
(a) culturing a cell transformed with the polynucleotide of claim 1 or a vector comprising the polynucleotide in culture medium under conditions wherein the polynucleotide is expressed; and
(b) recovering the antibody or antigen-binding fragment thereof from the cell or culture medium.