# US 10,946,104 B2 · Aberrant cell-restricted immunoglobulins provided with a toxic moiety

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- Number: US 10,946,104 B2
- Document ID: US10946104B2
- Status: Granted
- Kind: B2
- Application number: 14/372,094
- Filed: 2013-01-11
- Published: 2015-02-26
- Granted: 2021-03-16
- Earliest claimed: 2012-01-13
- Assignees: Apo-Tb.V.
- Applicants: Apo-T B.V.
- Inventors: Johan Renes; Paul Steverink; Ralph Alexander Willemsen
- Web page: https://patentgrep.com/patent/US10946104B2

## CPC

- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61K 47/6809: {Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6883: {Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy}
- A61P 35/00: Antineoplastic agents
- C07K 16/084: Papillomaviridae (F); Polyomaviridae (F), e.g. SV40, BK virus or JC virus
- C07K 16/085: Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/2884: {against CD44}
- C07K 16/30: from tumour cells
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 16/3092: {against tumour-associated mucins}
- C07K 16/32: against translation products of oncogenes
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- 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 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- 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)

## Abstract

Described are immunoglobulins provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. These immunoglobulins provided with a toxic moiety are preferably used in selectively modulating biological processes. The provided immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

## Claims

### Claim 1

An immunoglobulin conjugated to a toxic moiety comprising at least an immunoglobulin region that specifically binds to an MHC-I-MAGE peptide complex,
wherein the immunoglobulin region comprises a Vh domain comprising SEQ ID NO: 1;
wherein the MAGE peptide of the MHC-I-MAGE peptide complex is derived from intracellular MAGE associated with aberrant cells; and
wherein the MAGE peptide is a multi-MAGE epitope.

### Claim 2 (depends on 1)

The immunoglobulin conjugated to a toxic moiety according to claim 1, wherein the immunoglobulin region further comprises a Vl.

### Claim 3 (depends on 1)

The immunoglobulin conjugated to a toxic moiety of claim 1, wherein the MHC-I-MAGE peptide complex is specific for aberrant cells.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising:
the immunoglobulin conjugated to a toxic moiety of claim 1, and suitable diluents and/or excipients.

### Claim 5 (depends on 1)

A method of treating a host suffering from a disease associated with aberrant cells, the method comprising:
administering the immunoglobulin conjugated to a toxic moiety of claim 1 to the host, for the treatment of the host suffering from a disease associated with aberrant cells.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the toxic moiety is internalized into an aberrant cell of the host.

### Claim 7 (depends on 1)

A method of treating a subject determined to be suffering from cancer, the method comprising:
administering the immunoglobulin conjugated to a toxic moiety of claim 1 to the host to treat cancer.

### Claim 8 (depends on 7)

The method according to claim 7, wherein at least the toxic moiety is internalized into an aberrant cell of the subject.

### Claim 9 (depends on 3)

The immunoglobulin conjugated to a toxic moiety of claim 3, wherein the MAGE is MAGE-A.

### Claim 10 (depends on 1)

The immunoglobulin conjugated to a toxic moiety of claim 1, wherein the toxic moiety is a fusion protein fused to the immunoglobulin at the DNA level through a linking sequence.

### Claim 11 (depends on 1)

The immunoglobulin conjugated to a toxic moiety of claim 1, wherein the MHC-I-MAGE peptide complex is upregulated on aberrant cells.
