University of Pennsylvania

Zhiqiang Zhu

Mark I Greene

Zheng Cai

Douglas B Cines

Hongtao Zhang

Lian Lam

Provided herein are isolated antibodies or antibody fragments thereof that immunospecifically bind to platelet factor 4 (PF4). In some embodiments the isolated antibodies or antigen-binding fragments thereof comprise a light chain CDR and framework region comprising SEQ ID NO: 4 and a heavy chain CDR and framework region comprising SEQ ID NO: 10. Also provided herein are methods for treating heparin-induced thrombocytopenia (HIT) and methods for reducing the likelihood that subject will become afflicted with HIT. Further disclosed are uses of the isolated antibodies or antibody fragments in the treatment of HIT or the manufacture of compositions for the treatment of HIT.

Fully humanized anti-platelet factor 4 antibodies that treat heparin-induced thrombocytopenia

The present invention provides a mutant protein which has the same amino acid sequence of a wild type PF4 monomer except that (i) at least one amino acid of the wild type PF4 monomer has been deleted, (ii) at least one amino acid of the wild type PF4 monomer has been replaced by another amino acid, or (iii) a combination of such changes has been made. The present invention also provides methods of treating or reducing the likelihood of HIT, treating angiogenesis, treating abnormal cell growth, or affecting coagulation pathologies that lead to thrombus formation, by administering such mutant proteins to a patient.

Atomic description of immune complex that causes heparin-induced thrombocytopenia

The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants. The present invention also provides a mutant protein which has the same amino acid sequence of a wild type PF4 monomer except that (i) at least one amino acid of the wild type PF4 monomer has been deleted, (ii) at least one amino acid of the wild type PF4 monomer has been replaced by another amino acid, or (iii) a combination of such changes has been made. The present invention also provides methods of treating or reducing the likelihood of HIT, treating angiogenesis, treating abnormal cell growth, or affecting coagulation pathologies that lead to thrombus formation, by administering such mutant proteins to a patient.

Disclosed herein are multifunctional antigen-binding proteins comprising at least one multifunctional recombinant protein scaffold and at least one antigen-specific binding domain. Polynucleotides encoding the multifunctional antigen-binding proteins, vectors containing the disclosed polynucleotides, and cells that have been genetically engineered to express the polynucleotide are also provided. Methods of using the multifunctional antigen-binding proteins are disclosed.

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Philadelphia, PA, United States of America

Zhiqiang Zhu