# US 11,993,645 B2 · Compositions comprising R-Spondin (RSPO) surrogate molecules

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- Number: US 11,993,645 B2
- Document ID: US11993645B2
- Status: Granted
- Kind: B2
- Application number: 16/476,501
- Filed: 2018-01-11
- Published: 2020-01-23
- Granted: 2024-05-28
- Earliest claimed: 2017-01-11
- Assignees: The Board of Trustees of the Leland Stanford Junior University
- Applicants: The Board of Trustees of the Leland Stanford Junior University
- Inventors: Vincent Christopher Luca; Kenan Christopher Garcia
- Web page: https://patentgrep.com/patent/US11993645B2

## CPC

- C07K 16/18: against material from animals or humans
- C07K 14/5406: {IL-4}
- C07K 14/55: IL-2
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/3046: {Stomach, Intestines}
- 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)
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 16/40: against enzymes
- C07K 2317/31: multispecific
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/77: Internalization into the cell
- C07K 2319/00: Fusion polypeptide
- C07K 2319/21: containing a His-tag
- C07K 2319/75: containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
- C07K 2319/81: containing a Zn-finger domain for DNA binding
- 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)

## Abstract

R-spondin (RSPO) surrogate compositions and methods for their use are provided. RSPO surrogates of the invention comprise (i) a specific binding domain for Ring Finger Protein 43 (RNF43) or Zinc and Ring Finger Protein 3 (ZNRF3) and (ii) a cell targeting domain More specifically, wherein the specific binding domain for RNF43 or ZNRF3 is an antibody fragment, and wherein the cell targeting domain is a cytokine.

## Claims

### Claim 1

An RSPO surrogate composition that comprises:
(i) a specific binding domain for RNF43 or ZNRF3, wherein the specific binding domain for RNF43 or ZNRF3 is an antibody or antigen-binding fragment thereof; and
(ii) a cell-targeting domain, wherein the cell-targeting domain is a cytokine or growth factor that specifically binds a cell surface receptor.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the specific binding domain for RNF43 or ZNRF3 comprises 6 CDR sequences of Z6 or R5 binding sequences set forth in any one of SEQ ID NO:1-4.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the specific binding domain for RNF43 or ZNRF3 is a single-chain Fv (scFv) construct.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the cell-targeting domain is the or growth factor.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the cell-targeting domain is the cytokine.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the cytokine is IL-2 or IL-4.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the domains are fused through a flexible linker.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the domains are directly joined.

### Claim 9 (depends on 1)

The composition of claim 1, formulated with an effective dose of a Wnt agent.

### Claim 10 (depends on 1)

The composition of claim 1, joined to a Wnt agent.