Multispecific engineered biomolecules and uses thereof
AssigneeThe Regents of the University of California
InventorsAaron S. MEYER, Brian ORCUTT-JAHNS, Peter EMMEL
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Abstract
The present disclosure provides a multispecific multivalent biomolecule comprising two or more covalently linked cytokines or variants thereof, wherein at least one cytokine is signaling-competent such as the native cytokine or a signaling-competent variant thereof, and at least one of the same or different cytokine is signaling-deficient compared to its native cytokine. The multispecific multivalent biomolecule presented herein can be used to activate or suppress immune responses in a subject.
Claims71
A multispecific multivalent biomolecule comprising two or more covalently linked cytokines or variants thereof, wherein the biomolecule comprises at least a first cytokine or variant thereof, and at least a second cytokine or variant thereof, wherein:
- a. the first cytokine or variant thereof is a signaling-competent cytokine or a signaling-competent variant thereof;
- and
- b. the second cytokine or variant thereof is a same or different cytokine from the first cytokine, and is signaling-deficient compared to that of a native second cytokine.
The multispecific multivalent biomolecule of any one of claims 1-52, wherein the biomolecule comprises a dimer of two cross-linked SEQ ID NO:7, two cross-linked SEQ ID NO:20, a cross-linked SEQ ID NO:07 and SEQ ID NO:20, two cross-linked SEQ ID NO:22, two cross-linked SEQ ID NO:24, two cross-linked SEQ ID NO:29, two cross-linked SEQ ID NO:31, two cross-linked SEQ ID NO:35, a cross-linked SEQ ID NO:
- 29 and SEQ ID NO:20, a cross-linked SEQ ID NO:7 and SEQ ID NO:35, a cross-linked SEQ ID NO:31 and SEQ ID NO:7, a cross-linked SEQ ID NO:31 and SEQ ID NO:
- 20, a cross-linked SEQ ID NO:31 and SEQ ID NO:22, a cross-linked SEQ ID NO:
- 31 and SEQ ID NO:24, or a cross-linked SEQ ID NO:31 and SEQ ID NO:29.
A multispecific multivalent cytokine comprising any one of SEQ ID NOs:
- 07, 08, 09, 11, 13, 15, 17, 19, 20, 22, 24, 26, 29, 31, 33, 35 and 37.
A multispecific multivalent cytokine comprising a cross-linked dimer of any one of SEQ ID NOs:
- 07, 20, 22, 24, 29, 31, 35 or any homodimeric or heterodimeric combination thereof.
A nucleic acid molecule encoding any one of SEQ ID NOs:
- 07, 08, 09, 11, 13, 15, 17, 19, 20, 22, 24, 26, 29, 31, 33, 35 and 37.
A vector comprising a nucleic acid molecule encoding any one of SEQ ID NOs:
- 07, 08, 09, 11, 13, 15, 17, 19, 20, 22, 24, 26, 29, 31, 33, 35 and 37.
A nucleic acid molecule selected from any one of SEQ ID NOs:
- 30, 32, 34, 36 or 38.
A vector comprising a nucleic acid molecule selected from SEQ ID NOs:
- 30, 32, 34, 36 or 38.
A mRNA comprising a nucleic acid sequence selected from SEQ ID NOs:
- 30, 32, 34, 36 or 38.
Dependencies are inferred from the claim text.