Validating dynex network
Exemplary vascular targeting agents (VTAs) are described in U. Another effective version of the vascular targeting approach is to target a coagulation factor to a marker expressed or adsorbed within the tumor vasculature or stroma (Huang et al, 1997; U. An even more important advance would be the identification of a class of therapeutic agents with anti-cancer properties and therapeutic effects in other systems.The development of agents capable of treating both cancer and viral infections, two of the most significant medical challenges of this era, would be a remarkable and important breakthrough.Targeting the blood vessels of the tumors, rather than the tumor cells themselves, has certain advantages in that it is not likely to lead to the development of resistant tumor cells, and that the targeted cells are readily accessible. The delivery of coagulants, rather than toxins, to tumor vasculature has the further advantages of reduced immunogenicity and even lower risk of toxic side effects. This led to the development of new anti-PS and anti-PE immunoconjugates for delivering anti-cellular agents, toxins and coagulation factors to tumor blood vessels (U. The development of new naked antibodies with anti-cancer properties would be a particularly important advance, as this permits the same targeting moiety to be used both as a single-agent therapeutic and as a vascular targeting agent for the delivery of other drugs.Moreover, destruction of the blood vessels leads to an amplification of the anti-tumor effect, as many tumor cells rely on a single vessel for their oxygen and nutrients. 5,855,866, 5,965,132, 6,261,535, 6,051,230 and 6,451,312, which describe the targeted delivery of anti-cellular agents and toxins to markers of tumor vasculature. Therapeutic agents that have both anti-angiogenic and anti-vascular, i.e., tumor destructive, properties within the same molecule would be of great value.The composition of claim 61, wherein said anti-cancer agent is cytosine arabinoside, methotrexate, aminopterin, demecolcine, mithramycin, chlorambucil, melphalan, daunorubicin, doxorubicin, verapamil, tamoxifen, taxol, vincristine, vinblastine, etoposide, 5-fluorouracil (5FU), camptothecin, actinomycin-D, mitomycin C, cisplatin, bleomycin, a combretastatin or cyclophosphamide. The composition of claim 61, wherein said anti-cancer agent is a targeting agent- therapeutic agent construct comprising a therapeutic agent operatively linked to a targeting region that binds to an accessible component of a tumor cell or tumor stroma or to a surface- expressed, surface-accessible, surface-localized, cytokine-inducible or coagulant-inducible component of tumor vasculature or intratumoral vasculature.79.The composition of claim 71, wherein said duramycin peptide is operatively attached to a targeting protein, antibody, or antigen binding region thereof, that binds to a tumor cell, tumor vasculature or tumor stroma.89.
The composition of claim 1 , wherein said antibody comprises at least a first variable region that includes an amino acid sequence region having the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.28.
Use of a composition in accordance with any preceding claim in the manufacture of a medicament for treating macular degeneration, age-related macular degeneration, arthritis, rheumatoid arthritis, atherosclerosis, diabetic retinopathy, thyroid hypeφlasia, Grave's disease, hemangioma, neovascular glaucoma or psoriasis. 60/396,263, filed July 15, 2002, the disclosure of which application, including the specification, claims, drawings and sequences, is specifically incorporated herein by reference without disclaimer. Field of the Invention The present invention relates to the fields of aminophospholipid and anionic phospholipid biology, tumor blood vessels and viral infections.
SELECTED ANTIBODIES AND DURAMYCIN PEPTIDES BINDING TO ANIONIC PHOSPHOLIPIDS AND AMINOPHOSPHOLIPIDS AND THEIR USE IN TREATING VIRAL INFECTIONS AND CANCER BACKGROUND OF THE INVENTION The present application claims priority to co-pending U. It provides surprising new compositions, methods and combinations for tumor vasculature targeting and cancer treatment, for inhibiting viral entry and spread and for treating viral infections.
The composition of claim 26, wherein said antibody is operatively attached to said biological agent as a fusion protein prepared by expressing a recombinant vector that comprises, in the same reading frame, a DNA segment encoding said antibody operatively linked to a DNA segment encoding said biological agent.61.
The composition of claim 59, wherein said anti-cancer agent is a chemotherapeutic agent, radiotherapeutic agent, anti-angiogenic agent, apoptosis-inducing agent, anti-tubulin drug or a tumor-targeted chemotherapeutic agent, radiotherapeutic agent, anti-angiogenic agent, apoptosis-inducing agent or anti-tubulin drug.62.