# US 2022/0089679 A1 · Fusion protein with immunosuppressive activity

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- Number: US 2022/0089679 A1
- Document ID: US20220089679A1
- Status: Published application
- Kind: A1
- Application number: 17/422,113
- Filed: 2020-01-10
- Published: 2022-03-24
- Earliest claimed: 2019-01-11
- Assignees: Fundació Institut D'Investigació BiomèDica De Bell; Universitat De Barcelona
- Applicants: Fundació Institut D'Investigació BiomèDica De Bell; Universitat De Barcelona
- Inventors: Josep Maria GRINYO BOIRA; Oriol BESTARD MATAMOROS; Juan TORRAS AMBROS
- Web page: https://patentgrep.com/patent/US20220089679A1

## CPC

- C07K 14/70532: {B7 molecules, e.g. CD80, CD86}
- C12N 15/62: DNA sequences coding for fusion proteins
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides a compound comprising a fusion polypeptide of formula (I): R1-L-R2-Fc wherein R1, which is at the N-terminal end of the polypeptide, is PD-L2 or a PD1-binding fragment thereof, L is a peptide linker, R2 is CTLA-4 or a CD80/CD86-binding fragment thereof, and Fc, which is at the C-terminal end of the polypeptide, is an immunoglobulin Fc domain. The present invention also provides a dimer of the compound, a polynucleotide which encodes the polypeptide, a vector comprising the polynucleotide, a host cell which contains the polynucleotide, a composition and a kit comprising the compound. The invention also provides the compound or the dimer for use in therapy, diagnosis and prognosis, in particular for the treatment of autoimmune diseases or transplant rejection.

## Claims

### Claim 1

A compound comprising a fusion polypeptide of formula (I):
R1-L-R2-Fc (I)
wherein:
R1, which is at the N-terminal end of the polypeptide, is PD-L2 or a PD1-binding fragment thereof,
L is a peptide linker,
R2 is CTLA-4 or a CD80/CD86-binding fragment thereof, and
Fc, which is at the C-terminal end of the polypeptide, is an immunoglobulin Fc domain.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein the linker:
has a length from 5 to 50 amino acids; or, alternatively,
has at least a 50%, at least a 60%, at least a 70%, at least an 80% or at least a 90% of amino acidic residues, with respect to the total number of amino acidic residues forming the peptide linker, selected from non-polar and polar uncharged amino acids; or, alternatively,
has a length from 5 to 50 amino acids, wherein at least a 50%, at least a 60%, at least a 70%, at least an 80% or at least a 90% of the amino acids forming the peptide linker are selected from non-polar and polar uncharged amino acids; or, alternatively,
has a length from 5 to 50 amino acids, wherein at least a 50%, at least a 60%, at least a 70%, at least an 80% or at least a 90% of the amino acids forming the peptide linker are non-polar and polar uncharged amino acids; or, alternatively,
has a length from 5 to 50 amino acids, wherein at least a 50%, at least a 60%, at least a 70%, at least an 80% or at least a 90% of the amino acids forming the peptide linker are Gly and Ser; or, alternatively,
has an amino acid sequence with an identity of at least 85% with sequence SEQ ID NO: 4.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein:
R1 is the extracellular domain of PD-L2, R2 is the extracellular domain of CTLA-4, and the Fc comprises the hinge region, the CH2 domain, and the CH3 domain of human IgG; or alternatively,
the sequence of the fusion polypeptide has at least 85%, at least 90% or at least 95% identity with sequence SEQ ID NO: 5; or a 100% of identity with sequence SEQ ID NO: 5.

### Claim 4 (depends on 1)

A dimer comprising two subunits, wherein one or both subunits correspond(s) to the compound as defined in claim 1.

### Claim 5 (depends on 1)

The compound according to claim 1 or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound, wherein the compound further comprises a heterologous moiety.

### Claim 6 (depends on 1)

A polynucleotide which encodes the compound as defined in claim 1 or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound.

### Claim 7 (depends on 6)

A vector comprising the polynucleotide as defined in claim 6.

### Claim 8 (depends on 6)

A host cell which is transformed or transfected with the polynucleotide as defined in claim 6 or a vector comprising the polynucleotide.

### Claim 9 (depends on 8)

A cell culture comprising the host cell as defined in claim 8.

### Claim 10 (depends on 1)

A process for the production of a compound as defined in claim 1, comprising:
(a) culturing a host cell transformed or transfected with a polynucleotide which encodes the compound; or, alternatively,
(b) in vitro transcription and/or translation of the polynucleotide to express the compound; and
(c) isolating the expressed compound.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the compound as defined in claim 1 or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier or excipient.

### Claim 12 (depends on 1)

A kit comprising:
the compound as defined in claim 1; or
a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound; or
a pharmaceutical composition comprising: a therapeutically effective amount of the compound or a dimer comprising two subunits wherein at least one of the two subunits is one or both subunits correspond(s) to the compound, the pharmaceutical composition further comprising at least one pharmaceutically acceptable carrier or excipient; and
optionally, instructions for its use.

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15 (depends on 1)

A method for treating and/or preventing a disease selected from an autoimmune disease and transplant rejection, the method comprising administering to a subject in need thereof, a therapeutically effective amount of:
a compound as defined in claim 1; or
a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound; or
a pharmaceutical composition comprising: a therapeutically effective amount of the compound or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound, wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier or excipient.

### Claim 16 (depends on 1)

A method for inhibiting T cell activation in an isolated biological sample from a subject, the method comprising the step of contacting the isolated biological sample with:
a compound as defined in claim 1; or
a dimer comprising two subunits, wherein one or both subunits correspond(s) to the compound; or
a pharmaceutical composition comprising: a therapeutically effective amount of the compound or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound, wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier or excipient.

### Claim 17 (depends on 1)

A method of transplantation of a mammalian organ or tissue, the method comprising:
removing the organ or tissue from a donor;
contacting the organ or tissue with:
a compound as defined in claim 1; or
a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound; or
a pharmaceutical composition comprising:
a therapeutically effective amount of the compound or a dimer comprising two subunits wherein one or both subunits correspond(s) to the compound, wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier or excipient; and
transplanting said organ or tissue in the recipient.