Anti-CD30 antibodies
Inventors
Medin, Jeffrey A. • Faber, Mary L • TATE, EVERETT R. • Oldham, Robyn A. A.
Assignees
Medical College of Wisconsin • UVA Licensing and Ventures Group
Publication Number
US-12351639-B2
Publication Date
2025-07-08
Expiration Date
2039-09-24
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Abstract
The present invention provides novel antibodies and antigen binding fragments thereof that bind to human CD30. Also presented are single chain variable antibodies, chimeric antigen receptors and uses thereof. Methods of treating cancer are also disclosed.
Core Innovation
The invention provides novel isolated antibodies and antigen binding fragments capable of specifically binding human CD30, including monoclonal antibodies, single chain variable antibodies, and chimeric antigen receptors (CARs) containing CD30 binding domains. These antibodies have defined complementarity determining regions (CDRs) and sequences distinct from known antibodies such as AC10. They are characterized by their selective binding to CD30, a transmembrane glycoprotein expressed preferentially on activated lymphoid cells and certain tumor cells, and can be utilized in detecting CD30 expression, treating CD30-positive cancers, and stratifying patient populations.
The background highlights the problem that CD30 is an important target for treating hematological malignancies like Hodgkin's lymphoma (HL) and acute myeloid leukemia (AML), but existing therapies face challenges such as relapse and chemo-resistance. There is a low expression of CD30 on normal cells, which emphasizes the need for improved therapeutic antibodies that specifically target CD30-positive neoplastic cells to enhance treatment efficacy and potentially overcome resistance seen with current treatments.
To address this, the present invention discloses antibodies with unique CDRs and sequences that bind to epitopes on CD30 distinct from known antibodies like AC10. These antibodies include variants with at least 85% sequence similarity to identified sequences and can be formulated into compositions, used to inhibit tumor growth, or incorporated into CAR constructs to engineer effector cells for targeted cancer therapy. The invention also includes related nucleic acids, expression vectors, and methods for treatment and detection by using the novel antibodies and their fragments.
Claims Coverage
The claims establish 20 main inventive features focusing on novel antibodies, antigen binding fragments, scFv constructs, compositions, and CARs with specific CD30 binding domains defined by particular CDR sequences and sequence similarities.
Isolated antibodies and antigen binding fragments with specified CD30-binding CDR sequences
Provides isolated antibodies or fragments capable of binding human CD30 comprising defined light and heavy chain variable domains with CDR regions as per SEQ ID NOs: 2-4 and 6-8, or similar sequences with at least 85% similarity, covering five distinct sets of CDRs (claims 1).
Antibody formats including monoclonal, humanized, scFv, single domain, and chimeric antibodies
The antibodies or fragments can be monoclonal, humanized, single chain variable fragments, single domain antibodies, or chimeric antibodies, and can be engrafted in full IgG or scFv scaffolds, preferably of human origin (claims 2-4).
Single chain variable fragments (scFv) comprising linked light and heavy chains
Antigen binding fragments can be single chain variable fragments where light and heavy chain variable domains are linked via an amino acid linker, with scFv sequences shown in SEQ ID NOs: 42, 44, 46, 48, 50, and 52 or similar sequences (claims 5-6).
Pharmaceutical compositions comprising the CD30 specific antibodies or fragments
Compositions comprising the antibodies or antigen binding fragments with pharmaceutically acceptable carriers are claimed for formulation and administration (claim 7).
Isolated antibodies or fragments with higher sequence similarity thresholds for CDR regions
Claims extend to antibodies or fragments with at least 90%, 95%, or 98% similarity in CDR regions to the specified sequences for enhanced specificity and binding efficacy (claims 8-10).
Antibodies or fragments defined by light and heavy chain sequences or high sequence similarity thereof
Isolation includes antibodies comprising light and heavy chains with sequences or ≥90%, ≥95%, or ≥98% similarity to specific SEQ ID NOs: 1 and 5, 9 and 13, 17 and 21, 25 and 29, or 33 and 37 (claims 11-13).
Specific antibodies comprising exact light and heavy chain sequences
Claims cover antibodies comprising the exact amino acid sequences as per SEQ ID NOs: 1 and 5, 9 and 13, 17 and 21, 25 and 29, or 33 and 37 (claim 14).
scFv constructs defined by particular amino acid sequences with similarity thresholds
scFv molecules comprising sequences of SEQ ID NO: 42, 44, 46, 48, 50, or 52 or with at least 90%, 95%, or 98% similarity are claimed (claims 15-17).
Chimeric antigen receptor (CAR) constructs comprising CD30 binding domains with specified CDRs
CARs comprising CD30 binding domains with defined CDRL and CDRH regions, a hinge, transmembrane domain, co-stimulatory domain, and intracellular signaling domain including CD3 zeta, are claimed, where the CD30 binding domains correspond to one of five specified CDR sets or scFv (claims 18-19).
Isolated antibodies binding human CD30 with precise defined CDR and chain sequences
Specific claims cover isolated antibodies or fragments with exact CDR and variable domain sequences including those having exact light chain SEQ ID NO: 1 and heavy chain SEQ ID NO: 5 sequences and their related scFv sequences and scaffolds, including humanized and chimeric forms (claims 20-33).
Isolated antibodies or fragments with alternative defined CDR and sequences
Antibodies or fragments comprising light and heavy chain variable domains relating to a second set of sequences (e.g., SEQ ID NOs: 9 and 13 for light and heavy chains) with exact or similar sequences, including humanized, chimeric forms and scFv scaffolds (claims 34-43).
The claims comprehensively cover novel isolated anti-human CD30 antibodies and antigen binding fragments characterized by unique CDR sequences and variable domain sequences, their pharmaceutical compositions, scFv constructs, and chimeric antigen receptors comprising these binding domains. Different similarity thresholds are included to cover variants, and various antibody formats such as monoclonal, humanized, chimeric, and single chain antibodies are within the scope. Additionally, nucleic acids and vectors encoding these constructs and effector cells expressing the CARs are encompassed.
Stated Advantages
The antibodies specifically bind to CD30 and have unique epitopes distinct from existing antibodies such as AC10, enabling targeted therapy against CD30-positive cancers while minimizing effects on non-target cells.
The novel antibodies can be used in various formats, including CAR constructs, which facilitate engineering immune effector cells for improved cancer treatment.
The defined sequences and similarity thresholds allow for flexibility in design and humanization, enhancing therapeutic applicability and reducing immunogenicity.
The antibodies enable stratification of patients based on CD30 expression, aiding in diagnostic and treatment decision-making.
Documented Applications
Treatment of CD30-positive cancers such as Hodgkin lymphoma (HL), acute myeloid leukemia (AML), anaplastic large cell lymphoma, ovarian cancer, mesothelioma, skin squamous cell carcinoma, triple negative breast cancer, pancreatic cancer, small cell lung cancer, anal cancer, and thyroid carcinoma.
Methods of inhibiting growth of tumor cells expressing CD30 by contacting them with the antibodies or fragments thereof.
Use of the antibodies in chimeric antigen receptors to engineer immune effector cells (e.g., T cells) for targeted immunotherapy.
Detection of CD30-positive cells in samples from patients for diagnosis and patient stratification using flow cytometry, ELISA, immunohistochemistry, and related assays.
Pharmaceutical compositions for administration to patients, including antibody-drug conjugates with chemotherapeutic agents such as monomethyl auristatin E (MMAE).
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