Variant CD58 domains and uses thereof

Patent metadata

Field	Value
Publication number	US-12037378-B2
Application number	US-202017612993-A
Country	US
Kind code	B2
Filing date	May 19, 2020
Priority date	May 21, 2019
Publication date	Jul 16, 2024
Grant date	Jul 16, 2024

Abstract

The present disclosure provides CD2 binding molecules that specifically bind to CD2, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD2 binding molecules, and pharmaceutical compositions comprising the CD2 binding molecules and the conjugates. The disclosure further provides methods of using the CD2 binding molecules to modulate CD2 signaling in order to treat a variety of immune (e.g., autoimmune), inflammatory and proliferative disorders. The disclosure yet further provides recombinant host cells engineered to express the CD2 binding molecules and methods of producing the CD2 binding molecules by culturing the host cells under conditions in which the CD2 binding molecules are expressed.

First claim

What is claimed is:

1. A CD2 binding molecule comprising a variant CD58 domain whose amino acid sequence comprises the amino acid sequence of SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO: 11.

2. The CD2 binding molecule of claim 1 , which is a bispecific binding molecule (BBM).

3. A conjugate comprising (a) the CD2 binding molecule of claim 1 , and (b) an agent.

4. The conjugate of claim 3 , wherein the agent is a therapeutic agent, a diagnostic agent, a masking moiety, a cleavable moiety, a stabilizing moiety or any combination thereof.

5. A pharmaceutical composition comprising the CD2 binding molecule of claim 1 and a pharmaceutically acceptable excipient.

6. A method of treating an immune or inflammatory disorder, comprising administering to a subject in need thereof the CD2 binding molecule of claim 1 .

7. A method of treating a subject with cancer, comprising administering to a subject suffering from cancer an effective amount of the CD2 binding molecule of claim 1 .

8. The method of claim 7 , wherein the cancer is HER2+ cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, Burkitt Lymphoma, carcinoma of unknown primary origin, cardiac tumor, cervical cancer, chordoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myeloproliferative neoplasm, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, ductal carcinoma, embryonal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoma, Ewing sarcoma, eye cancer, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestational trophoblastic disease, glioma, head and neck cancer, hairy cell leukemia, hepatocellular cancer, histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumor, Kaposi sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, leukemia, lip and oral cavity cancer, liver cancer, lobular carcinoma in situ, lung cancer, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, midline tract carcinoma involving NUT gene, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasm, nasal cavity and para-nasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytomas, pituitary tumor, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell cancer, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary gland cancer, Sezary syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord tumor, stomach cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvar cancer, or Wilms tumor.

9. A nucleic acid or plurality of nucleic acids encoding the CD2 binding molecule of claim 1 .

10. A cell engineered to express the CD2 binding molecule of claim 1 .

11. A cell comprising one or more nucleic acid sequences encoding the CD2 binding molecule of claim 1 under the control of one or more promoters.

12. A method of producing a CD2 binding molecule, comprising:
(a) culturing the cell of claim 10 or claim 11 in conditions under which the CD2 binding molecule is expressed; and
(b) recovering the CD2 binding molecule from the cell culture.

13. The CD2 binding molecule of claim 1 , wherein the amino acid sequence of the variant CD58 domain comprises the amino acid sequence of SEQ ID NO:8.

14. The CD2 binding molecule of claim 1 , wherein the amino acid sequence of the variant CD58 domain comprises the amino acid sequence of SEQ ID NO:9.

15. The CD2 binding molecule of claim 1 , wherein the amino acid sequence of the variant CD58 domain comprises the amino acid sequence of SEQ ID NO:10.

16. The CD2 binding molecule of claim 1 , wherein the amino acid sequence of the variant CD58 domain comprises the amino acid sequence of SEQ ID NO:11.

Assignees

• Novartis Ag

Inventors

• Brannetti Barbara
• Chelur Dattananda
• Granda Brian
• Hong Connie

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K14/7051

  T-cell receptor (TcR)-CD3 complex · CPC title

• C07K14/70528 Primary

  CD58 · CPC title