IP Library Granted Patent US 12,648,964
Granted Patent B2
US 12,648,964 · App. 19/019,111 · Granted Jun 9, 2026

Chimeric Tim receptors and uses thereof

Inventors: Daniel Mark Corey (Menlo Park, CA); Nathan Kipniss (San Francisco, CA)
Assignee: CERO THERAPEUTICS HOLDINGS, INC.
A61K35/17A61K31/519A61K40/11A61K40/421A61P35/00C07K14/4727C07K14/70503C07K2319/03
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Quick Facts
Patent No.
US 12,648,964
App. No.
19/019,111
Granted
Jun 9, 2026
Kind
B2
Abstract

The present disclosure relates to chimeric Tim receptors, host cells modified to include chimeric Tim receptor molecules, and methods of making and using such receptor molecules and modified cells.

Claims (25)

1 . A chimeric engulfment receptor comprising a single chain chimeric protein, the single chain chimeric protein comprising:

(a) an extracellular domain comprising a binding domain comprising: a Tim4 IgG V domain and a Tim4 mucin domain;

(b) an intracellular signaling domain, wherein the intracellular signaling domain comprises a CD28 signaling domain, a CD3ζ signaling domain, and a TLR2 signaling domain; and

(c) a CD28 transmembrane domain positioned between and connecting the extracellular domain and the intracellular signaling domain.

2 . The chimeric engulfment receptor of claim 1 , wherein the binding domain comprises the amino acid sequence of SEQ ID NO:2.

3 . The chimeric engulfment receptor of claim 1 , wherein the binding domain comprises the amino acid sequence of SEQ ID NO:2.

4 . The chimeric engulfment receptor of claim 1 , wherein the CD28 transmembrane domain comprises the amino acid sequence of SEQ ID NO:7.

5 . The chimeric engulfment receptor of claim 1 , wherein the CD28 signaling domain comprises the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:26.

6 . The chimeric engulfment receptor of claim 1 , wherein the CD3ζ signaling domain comprises the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:27.

7 . The chimeric engulfment receptor of claim 1 , wherein the TLR2 signaling domain comprises the amino acid sequence of SEQ ID NO: 122.

8 . The chimeric engulfment receptor of claim 1 , wherein the chimeric engulfment receptor comprises from N-terminus to C-terminus: a Tim4 signal peptide comprising the amino acid sequence of SEQ ID NO:118; a Tim4 binding domain comprising the amino acid sequence of SEQ ID NO:42; a CD28 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 7; a CD28 signaling domain comprising the amino acid sequence of SEQ ID NO:4; a CD3ζ signaling domain comprising the amino acid sequence of SEQ ID NO:27; and a TLR2 signaling domain comprising the amino acid sequence of SEQ ID NO:122.

9 . The chimeric engulfment receptor of claim 1 , wherein the chimeric engulfment receptor comprises the amino acid sequence of SEQ ID NO:128 or SEQ ID NO: 129.

10 . A polynucleotide encoding the chimeric engulfment receptor of claim 1 .

11 . A vector comprising the polynucleotide of claim 10 .

12 . An engineered immune cell comprising the vector of claim 11 .

13 . The engineered immune cell of claim 12 , wherein the immune cell is a T cell.

14 . The engineered immune cell of claim 13 , wherein the T cell is a CD4+T cell, a CD8+T cell, or a CD4+/CD8+T cell.

15 . The engineered immune cell of claim 12 , wherein the immune cell is a human immune cell.

16 . A pharmaceutical composition comprising the engineered immune cell of claim 12 and a pharmaceutically acceptable excipient.

17 . A method of treating cancer in a subject, comprising administering an effective amount of the engineered immune cell of claim 12 to the subject.

18 . The method of claim 17 , wherein the cancer is breast cancer; prostate cancer; ovarian cancer; cervical cancer; skin cancer; pancreatic cancer; colorectal cancer; renal cancer; liver cancer; brain cancer; lymphoma; leukemia; lung cancer; adenocarcinoma of the breast; adenocarcinoma of the prostate; and adenocarcinoma of the colon; a form of bronchogenic carcinoma of the lung; myeloid leukemia; melanoma; hepatoma; neuroblastoma; papilloma; apudoma; choristoma; branchioma; malignant carcinoid syndrome; carcinoid heart disease; Walker carcinoma; basal cell carcinoma; basosquamous carcinoma; Brown-Pearce carcinoma; ductal carcinoma; Ehrlich tumor carcinoma; Krebs 2 carcinoma; Merkel cell carcinoma; mucinous carcinoma; non-small cell lung carcinoma; oat cell carcinoma; papillary carcinoma; scirrhous carcinoma; bronchiolar carcinoma; squamous cell carcinoma; transitional cell carcinoma; a histiocytic disorders; malignant histiocytosis; Hodgkin's disease; non-Hodgkin's lymphoma; plasmacytoma; multiple myeloma; chronic myeloid leukemia (CML); reticuloendotheliosis; chondroblastoma; chondroma; chondrosarcoma; fibroma; fibrosarcoma; giant cell tumor; histiocytoma; lipoma; liposarcoma; mesothelioma; myxoma; myxosarcoma; osteoma; osteosarcoma; chordoma; craniopharyngioma; dysgerminoma; hamartoma; mesenchymoma; mesonephroma; myosarcoma; ameloblastoma; cementoma; odontoma; teratoma; thymoma; trophoblastic tumor; adenoma; cholangioma; cholesteatoma; cyclindroma; cystadenocarcinoma; cystadenoma; granulosa cell tumor; gynandroblastoma; hidradenoma; islet cell tumor; Leydig cell tumor; sertoli cell tumor; theca cell tumor; leimyoma; leiomyosarcoma; myoblastoma; myomma; rhabdomyoma; rhabdomyosarcoma; ependymoma; ganglioneuroma; glioma; medulloblastoma; meningioma; neurilemmoma; neuroepithelioma; neurofibroma; neuroma; paraganglioma; paraganglioma nonchromaffin; angiokeratoma; angiolymphoid hyperplasia with eosinophilia; angioma sclerosing; angiomatosis; glomangioma; hemangioendothelioma; hemangioma; hemangiopericytoma; hemangiosarcoma; lymphangioma; lymphangiomyoma; lymphangiosarcoma; pinealoma; carcinosarcoma; chondrosarcoma; cystosarcoma phyllodes; leukosarcoma; sarcoma; neoplasms; neurofibromatosis; cervical dysplasia; peritoneal cancer; B-cell cancers; B-cell lymphoma central nervous system lymphoma; acute lymphoblastic leukemia (ALL); chronic lymphocytic leukemia (CLL); acute myeloid leukemia (AML); Hairy cell leukemia; B cell blast transformation of chronic myeloid leukemia; myeloma; small lymphocytic lymphoma; B-cell prolymphocytic leukemia; lymphoplasmacytic lymphoma; splenic marginal zone lymphoma; plasma cell myeloma; solitary plasmacytoma of bone; extraosseous plasmacytoma; extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue; nodal marginal zone B-cell lymphoma; follicular lymphoma; mantle cell lymphoma; diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma; intravascular large B-cell lymphoma; primary effusion lymphoma; Burkitt's lymphoma/leukemia; B-cell proliferations of uncertain malignant potential; lymphomatoid granulomatosis; or post-transplant lymphoproliferative disorder.

19 . The method of claim 17 , wherein the method further comprises administering an additional therapeutic agent to the subject.

20 . The method of claim 19 , wherein the additional therapeutic agent comprises radiation, cellular immunotherapy, antibody, immune checkpoint molecule inhibitor, chemotherapy, hormone therapy, peptide, antibiotic, anti-viral agent, anti-fungal agent, anti-inflammatory agent, UV light therapy, electric pulse therapy, high intensity focused ultrasound therapy, oncolytic virus therapy, a small molecule therapy, or any combination thereof.

21 . The method of claim 19 , wherein the additional therapeutic agent comprises an angiogenesis inhibitor, a VEGF pathway inhibitor, tyrosine kinase inhibitor, an EGF pathway inhibitor, receptor tyrosine kinase inhibitor, growth factor inhibitor, GTPase inhibitor, serine/threonine kinase inhibitor, transcription factor inhibitor, B-Raf inhibitor, RAF inhibitor, MEK inhibitor, mTOR inhibitor, EGFR inhibitor, ALK inhibitor, ROS1 inhibitor, BCL-2 inhibitor, PI3K inhibitor, VEGFR inhibitor, BCR-ABL inhibitor, MET inhibitor, MYC inhibitor, ABL inhibitor, HER2 inhibitor, BTK inhibitor, H-RAS inhibitor, K-RAS inhibitor, PDGFR inhibitor, TRK inhibitor, c-KIT inhibitor, c-MET inhibitor, CDK4/6 inhibitor, FAK inhibitor, FGFR inhibitor, FLT3 inhibitor, IDH1 inhibitor, IDH2 inhibitor, PDGFRA inhibitor, or RET inhibitor.

22 . The method of claim 21 , wherein the BTK inhibitor is ibrutinib, pirtobrutinib (Loxo-305), tirabrutinib (ONO-4059), tolebrutinib, evobrutinib, fenebrutinib (GDC-0853), acalabrutinib, spebrutinib, zanubrutinib (BGB-3111), HM71224, or M7583.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2025
From: COREY, DANIEL MARK; KIPNESS, NATHAN
To: CERO THERAPEUTICS, INC.
Reel/Frame 072188/0658 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2025
From: CERO THERAPEUTICS, INC.
To: CERO THERAPEUTICS HOLDINGS, INC.
Reel/Frame 072188/0668 →
Continuity (4)
Continuation 18041195
Provisional Application 63226643 · Jul 28, 2021
Provisional Application 63066085 · Aug 14, 2020
Related Publication 20250195575A1 · Jun 19, 2025
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