Abstract: A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibiting improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, a targeting ligand, or another active or therapeutic compound. IGF1 variants were shown to have improved ability to induce skeletal muscle hypertrophy relative to native IGF1.

Abstract: Methods of treating diabetes in mammals, particularly humans, by blocking or inhibiting VEGF-mediated activity. A preferred inhibitor of VEGF-mediated activity is a VEGF antagonist such as the VEGF fusion protein trap of SEQ ID NO:2 capable of binding and blocking VEGF. The method of the invention may be combined with other therapies, such as with insulin therapy.

Abstract: Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.

Abstract: Formulations of an interleukin-1 (IL-1) antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the IL-1 antagonist is an IL-1 trap composed of a dimer of two fusion protein having an amino acid sequence selected from the group consisting of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26. Most preferably, the fusion protein has the sequence of SEQ ID NO:10.

Abstract: Methods of treating, inhibiting, or ameliorating arthritis, including rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, or juvenile rheumatoid arthritis, in a human subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein arthritis inhibited, or ameliorated. The IL-1 antagonist is an IL-1-specific fusion protein comprising an IL-1 binding portion of the extracellular domain of human II-1RAcP, an IL-1 binding portion of the extracellular domain of human IL-1RI, and a multimerizing component antagonist, preferably comprising a sequence selected from the group consisting of SEQ ID NO:4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, or a substantially identical sequence.

Abstract: A targeting fusion protein comprising a component that comprises a (i) ligand or derivative or fragment thereof that binds a pre-selected target surface protein, such as a receptor, and (ii) an active agent or therapeutic agent(s), and further optionally (iii) a multimerizing component and/or (iv) a signal sequence. In a preferred embodiment, the targeting fusion polypeptide targets muscle and is useful to treat a muscle-related disease or condition, such as muscle atrophy.

Abstract: Methods for treating a human patient suffering from a brain tumor, including glioblastoma, by administering an effective amount of a vascular endothelial growth factor (VEGF) inhibitor to the human patient. The VEGF inhibitor is a VEGF antagonist protein comprising a dimeric protein having two fusion polypeptides having the sequence of SEQ ID NO:2.

Abstract: Disclosed are compositions and methods for treating a disease or condition related to angiogenesis with a vascular endothelial growth factor (VEGF) inhibitor and one or more anti-hypertensive agent(s). The method of the invention is useful for preventing the development of hypertension and/or reducing hypertension in a subject treated with a VEGF inhibitor.

Abstract: Methods of treating cancer and/or reducing or inhibiting tumor growth in a subject in need thereof, comprising administering pharmaceutical composition comprising a vascular endothelial cell growth factor (VEGF) antagonist, such as a VEGF trap, an anti-proliferative agent, such as taxol, and a pharmaceutically acceptable carrier.

Abstract: Methods of regressing or inhibiting a tumor in a subject by administering an agent capable of blocking, inhibiting, or ameliorating vascular endothelial growth factor (VEGF)-mediated activity to a subject in need thereof such that the tumor is regressed or inhibited. The method of the invention results in a reduction of tumor size and inhibition of tumor metastases. This method is particularly useful for patients suffering from bulky, metastatic cancers.

Abstract: A method of treating a human patient suffering from cancer, comprising administering an effective amount of a vascular endothelial growth factor (VEGF) trap antagonist to the human patient, the method comprising: (a) administering to the patient an initial dose of at least approximately 0.3 mg/kg of the VEGF antagonist; and (b) administering to the patient a plurality of subsequent doses of the VEGF antagonist in an amount that is approximately the same or less of the initial dose, wherein the subsequent doses are separated in time from each other by at least one day. The methods of the invention are useful for treating a human cancer selected from the group consisting of renal cell carcinoma, pancreatic carcinoma, breast cancer, prostate cancer, colorectal cancer, malignant mesothelioma, multiple myeloma, ovarian cancer, and melanoma. The invention is further useful for treating a condition which benefits from the reduction of VEGFA and placental growth factor (PLGF).

Abstract: Methods of treating anemic disorders in human subjects comprising administering a VEGF antagonist comprising a fusion polypeptide having an immunoglobulin-like (Ig) domain 2 of the VEGF receptor Flt1 and Ig domain 3 of the VEGF receptor Flk1 or Flt4, and a multimerizing component. Further included are methods of preventing anemia, increasing hematocrit levels, and increasing or stimulating erythropoietin, particularly in subjects being treated for cancer with chemotherapeutic agents and/or radiation.

Abstract: The invention provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.

Abstract: Modified chimeric polypeptides with improved pharmacokinetics and improved tissue penetration are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.

Abstract: Methods of reducing or treating angiogenesis and/or inflammation associated with eye injury in a subject in need thereof, comprising administering an agent capable of blocking or inhibiting vascular endothelial growth factor (VEGF) are provided. The methods are useful for inhibiting or ameliorating eye injury, particularly acute or subacute corneal injury and feature local administration (for example, subconjunctival injection or eye drops).

Abstract: Modified chimeric polypeptides with improved pharmacokinetics and improved tissue penetration are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.

Abstract: Modified chimeric polypeptides with improved pharmacokinetics are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.

Abstract: Methods of preventing, reducing, or treating corneal transplant rejection to improve transplant survival in a high risk subject comprising administering an agent capable of blocking or inhibiting vascular endothelial growth factor (VEGF) are provided. The methods are useful for inhibiting or preventing corneal transplant rejection in a human subject who is the recipient of a transplanted cornea.

Abstract: Methods of preventing, reducing, or treating corneal transplant rejection to improve transplant survival in a subject in need thereof comprising administering an agent capable of blocking or inhibiting vascular endothelial growth factor (VEGF) are provided. The methods are useful for inhibiting or preventing corneal transplant rejection in a human subject who is the recipient of a transplanted cornea.

Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant or complete contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.