Abstract: The present invention provides methods and compositions that permit controlled and prolonged drug release in vivo. The compounds are either prodrugs with tunable rates of release, or conjugates of the drug with macromolecules which exhibit tunable controlled rates of release.

Abstract: The present invention relates to methods and compositions for the treatment of cancer. Some embodiments include methods of treating cancer comprising administering a chemotherapeutic agent associated with albumin, administering a second chemotherapeutic agent; and administering a third chemotherapeutic agent.

Abstract: The present invention provides methods and compositions for treating pancreatic cancer in an individual who has been previously treated for pancreatic cancer (e.g., gemcitabine-based therapy) by administering a composition comprising nanoparticles that comprise a taxane and an albumin. The invention also provides combination therapy methods of treating pancreatic cancer (for example, in an individual who has been previously treated for pancreatic cancer) comprising administering to an individual an effective amount of a composition comprising nanoparticles that comprise a taxane and an albumin and another agent.

Abstract: The present invention provides methods and compositions for treating non-small-cell lung cancer (NSCLC) by administering a) a composition comprising nanoparticles that comprise paclitaxel and an albumin and b) a platinum-based agent (e.g., carboplatin). The present application also provides methods of treating prostate cancer by administering to the individual a) an effective amount of a composition comprising nanoparticles comprising docetaxel and an albumin; and b) an effective amount of a steroid.

Abstract: The present invention relates to biomarkers for preeclampsia as well as treatment of this disease. In particular, the invention relates to methods for diagnosis or aiding in the diagnosis of preeclampsia of a pregnant female mammal to detect elevated levels of free haemoglobin, particularly free fetal haemoglobin. This facilitates and makes possible early diagnosis and clinical intervention when a preeclamptic condition is found. In addition, the invention relates to a method to treat female mammals with preeclampsia with the purpose to reverse the pathological conditions associated with this disease.

Abstract: Provided herein are multifunctional heteromultimer proteins. In specific embodiments is a heteromultimer comprising: at least two polypeptide constructs, each polypeptide construct comprising at least one cargo polypeptide attached to a transporter polypeptide, said transporter polypeptides derived from a monomeric native protein such that said monomeric constructs associate to form the heteromultimer and said transporter polypeptides associate to form a quasi-native structure of the monomeric native protein or analog thereof. These therapeutically novel molecules encompass heteromultimers comprising constructs that function as scaffolds for the conjugation or fusion of therapeutic molecular entities (cargo polypeptides) resulting in the creation of bispecific or multivalent molecular species. Provided herein is a method for creation of bispecific or multivalent molecular species.

Abstract: The present invention provides methods and compositions for treating bladder cancer, including metastatic bladder cancer and non-muscle-invasive bladder cancer, by administering a composition comprising nanoparticles that comprise a taxane and an albumin.

Abstract: A pharmaceutical combined preparation containing a therapeutic protein having SH-groups which are nitrosated and a compound containing thiol groups and having an average molecular weight of at most 10,000.

Abstract: A biologically active complex comprising either a polypeptide having the sequence of a variant of a naturally occurring protein, wherein said polypeptide is at least partially unfolded as compared to the said naturally occurring protein; or a peptide of up to 50 amino acids, for instance a fragment of the naturally occurring protein or a variant thereof; and a pharmaceutically acceptable salt of a fatty acid or lipid. The complexes of the invention demonstrate a novel mode of action, that gives rise to opportunities for the development of further active agents and screening methods.

Abstract: The present invention relates to methods and compositions for treating cancer. Some embodiments include methods comprising increasing expression of a nucleic acid encoding secreted protein acidic and rich in cysteine (SPARC) protein or SPARC protein or the level or activity of SPARC protein and administering a chemotherapeutic agent to a subject in need thereof.

Abstract: The present invention relates to the novel use of prostacyclin analogs for prevention and/or treatment of capillary leakage during surgery. The treatment of the present invention mediates discrete or minimal effects on haemostasis and vasodilation. Thus the present invention provides prostacyclin and analogs thereof for treatment which prevents capillary leakage while minimizing the risk of bleeding. The present invention further provides pharmaceutical compositions and kits of parts comprising prostacyclin or analogs thereof, and methods for treatment.

Abstract: A thiol-yne polymeric material and methods for producing said polymers are disclosed. The material is produced by the radically mediated polymerization of monomers having alkyne and thiol functional groups. The alkyne moiety, internal or terminal, may react with one or two thiols. Degradable monomers may be used to form degradable polymers.

Abstract: The invention comprises the use of LGF in the production of medicinal products that can be used in the pleiotropic tissue regeneration of one or more damaged tissues, in which at least one of the damaged tissues forms part of the central nervous system and the medicinal product is intended to be administered systemically. The invention is based on the fact that intraperitoneal administration of LGF can promote a positive effect on a Parkinson's disease model. As such, in a preferred embodiment of the invention, the medicinal product is intended for the treatment of Parkinson's disease, particularly when the medicinal product is intended for humans.

Abstract: The invention describes albumin fusion proteins comprising growth hormone and serum albumin. The invention also describes nucleic acid molecules encoding the albumin fusion proteins of the invention, as well as vectors containing these nucleic acid molecules, host cells transformed with these vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally, the invention describes compositions comprising the albumin fusion proteins, and methods of treating patients in need of growth hormone, comprising administering the albumin fusion proteins of the invention.

Abstract: Here, we present a photodegradable microparticle system that can be employed to entrap and deliver bioactive proteins to cells during culture. By using a photosensitive delivery system, experimenters can achieve a wide variety of spatiotemporally regulated release profiles with a single microparticle formulation, thereby enabling one to probe many questions as to how protein presentation can be manipulated to regulate cell function. Photodegradable microparticles were synthesized via inverse suspension polymerization with a mean diameter of 22 ?m, and degradation was demonstrated upon exposure to several irradiation conditions. The protein-loaded depots were incorporated into cell cultures and release of bioactive protein was quantified during the photodegradation process. This phototriggered release allowed for the delivery of TGF-?1 to stimulate PE25 cells and for the delivery of fluorescently labeled Annexin V to assay apoptotic 3T3 fibroblasts during culture.

Abstract: The present disclosure relates to albumin fusion protein including an angiogenesis inhibiting peptide, or a fragment or variant thereof, and albumin, or a fragment or variant thereof. The fusion proteins exhibit extended shelf-life and/or extended or therapeutic activity in solution. The disclosure includes therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits, as well as nucleic acid molecules encoding the albumin fusion proteins, vectors containing these nucleic acids, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins using these nucleic acids, vectors, and/or host cells. The disclosure further relates to compositions and methods for inhibiting proliferation of vascular endothelial cells and tumor angiogenesis induced cell fusion.

Abstract: Provided are method of generating a fiber from a globular protein such as albumin. Also provided are albumin fibers and fabrics and methods of using same for bonding a damaged tissue or for ex vivo or in vivo formation of a tissue.

Abstract: A pharmaceutical composition comprising a lipid component; an amphiphilic emulsifier; and a polar liquid carrier. The lipid component and the amphiphilic emulsifier form free-moving lipid-carrying micelles (LMs) in the polar liquid carrier. The pharmaceutical composition is free of hemoglobin and fluorocarbon and can be used for treating conditions related to lack of blood supply and to raise the blood pressure.

Abstract: In one embodiment, the invention provides a method of suppressing, inhibiting, preventing, or treating conjunctivitis in a subject, comprising the step of administering an effective amount of a lipid or phospholipid moiety bound via an ester or amide bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof to a subject with conjunctivitis.

Abstract: There is provided a fusion protein comprising albumin and retinol-binding protein, which can be used for preventing or treating fibrotic diseases. The fusion protein, in which albumin and a retinol-binding protein (RBP) are bound together, induces the formation of cytoplasmic lipid droplets in stellate cells and returns the shape of activated stellate cells to the previous shape thereof before activation. Therefore, the fusion protein can be effectively used in preventing or treating fibrotic diseases occurring in the liver, pancreas, lungs, or other organs.

Abstract: A medical composition is described in which a synthetic polymer substrate and a composition mainly composed of a biopolymer directly adhere to each other due to dissolution of the surfaces thereof. The medical composition allows one to attach a biopolymer composition to a synthetic polymer substrate without the use of a toxic adhesive.

Abstract: The present invention provides a recombinant fusion protein which stimulates the rejuvenation and reactivation of skin and epidermal cells for improving skin appearance, smoothing wrinkles and freckles, and whitening skin. Particularly, the present invention provides various types of products for improving skin, which contain recombinant fusion protein of human serum albumin (HSA) with cytokine peptides (EGF, FGF, KGF, HGH, HGF, PDGF, GCSF, interferon, IL-11 or IGF) by genetic engineering technology. The fusion protein can be used independently or in a combination or combination with yeast fermentation products, or with varied emulsifiers, thickeners, moisturizer, preservatives, yeasts and ferments.

Abstract: The invention provides methods for treating spondylarthropathy with antagonists of MDL-1 alone or in combination with IL-23 antagonists.

Abstract: Non-natural albumin binding domains, polynucleotides encoding thereof and methods of making and using these domains and polynucleotides are useful in controlling the half-life of therapeutic molecules for patients.

Abstract: Provided herein is combination therapy containing an anti-hyaluronan agent, such as a polymer-conjugated hyaluronan-degrading enzyme, and a tumor-targeted taxane, and optionally a further chemotherapeutic agent such as a nucleoside analog. The combination therapy can be used in methods of treating cancers, and in particular solid tumor cancers.

Abstract: The invention relates to a composition comprising albumin and a therapeutic agent, particularly a gene therapy vector. The composition is useful in the treatment of glioma.

Abstract: The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

Abstract: A method for treating conditions related to lack of blood supply with a lipid based resuscitation fluid is disclosed. The resuscitation fluid contains a lipid component and an aqueous carrier. The lipid component forms an emulsion with the aqueous carrier. The resuscitation fluid can be used to increase the blood pressure and to carry oxygen to tissues. The resuscitation fluid can also be used for preserving the biological integrity of donor organs for transplantation.

Abstract: Tissue scaffolds of polymer microfiber or nanofiber mesh which release an active agent supportive of alignment, proliferation and matrix deposition of selected musculoskeletal cell over time are provided. Methods for production and use of these tissue scaffolds in treatment of musculoskeletal tissue injuries are also provided.

Abstract: This document relates to methods and materials for treating multiple myeloma. For example, methods and materials for using albumin-bound paclitaxel composition (e.g., Abraxane®, a paclitaxel albumin-stabilized nanoparticle formulation) to treat multiple myeloma are provided.

Abstract: Disclosed are water soluble polymeric conjugates comprising the structure POLY-[Y—S—S-A]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 2, S—S is a disulfide group attached to an sp3 hybridized carbon of Y; and A is a covalently linked residue of a pharmacologically active molecule. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are polymeric reagents useful to prepare such conjugates, and methods of their formation and use.

Abstract: Methods, compositions, systems, devices and kits are provided for preparing and using a multi-layer polymeric microstructure composition for delivering a therapeutic agent to a subject. In various embodiments, the therapeutic agent includes at least one selected from the group of: a drug, a protein, a sugar, a carbohydrate, and a nucleotide sequence. In related embodiments, the composition is a fiber, a suture, a sphere, an implant, or a scaffold.

Abstract: The invention provides multiparametric anti-SPARC antibody-based techniques for treating cancers as well as determining prognosis and predicting the response to therapy, including chemotherapy, radiotherapy, surgical therapy and combination therapies.

Abstract: The present invention provides methods and compositions for treating bladder cancer, including metastatic bladder cancer and non-muscle-invasive bladder cancer, by administering a composition comprising nanoparticles that comprise a taxane and an albumin.

Abstract: The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Abstract: Provided are method of generating a fiber from a globular protein such as albumin. Also provided are albumin fibers and fabrics and methods of using same for bonding a damaged tissue or for ex vivo or in vivo formation of a tissue.

Abstract: A method of improving the efficacy of a blood transfusion into a subject is provided comprising administering a composition comprising an EAF PEGylated-blood protein into the subject, prior to, during, or subsequent to the blood transfusion.

Abstract: The present disclosure provides a method for treating and/or preventing nephrotic syndrome, such as but not limited to MCD and MN, and conditions related to nephrotic syndrome, such as but not limited to, proteinuria and edema, as well as diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomerular disease. The present disclosure further provides methods for reducing proteinuria and other disease states as discussed herein. Such methods comprise the therapeutic delivery of an Angptl4 polypeptide or Angptl4 polypeptide derivative to a subject.

Abstract: Provided are method of generating a fiber from a globular protein such as albumin. Also provided are albumin fibers and fabrics and methods of using same for bonding a damaged tissue or for ex vivo or in vivo formation of a tissue.

Abstract: The present invention concerns the use of polychalcogenide compositions on cells, tissue, organs, and organisms to enhance their survivability. It includes compositions, compounds, methods, articles of manufacture and apparatuses for enhancing survivability and for protecting them from or treating them for injury or damage. In specific embodiments, there are also therapeutic methods and apparatuses for hypoxic/ischemic injury, organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer using the polychalcogenide compositions described.

Abstract: Techniques, methods and lavages are disclosed for prevention or treatment of shock, particularly cecal ligation or cecal inoculation shock, by administering a specific therapeutic agent, which is able to use smaller volumes of reagent to achieve partial to complete inhibition, than other previously described techniques. The agent includes a combination of enzyme inhibitor, cytotoxic lipid binding protein, and antibiotic.

Abstract: New designed repeat proteins with binding specificity for serum albumin are described, as well as nucleic acids encoding such serum albumin binding proteins, pharmaceutical compositions comprising such proteins, the use of such proteins to modify the pharmacokinetics of therapeutic relevant polypeptides and the use of such proteins in the treatment of diseases. The repeat proteins of the invention have a substantially increased half-life in plasma compared to proteins not binding serum albumin.

Abstract: The present invention provides an albumin polymer and a process of making an albumin polymer, the process comprising breaking instrinsic disulfide bridges in albumin with a reducing agent and crosslinking inter- and intra-molecular disulfide bridges so as to form the polymer. The present invention also provides PEGylated albumin polymers and methods of making PEGylated albumin polymers, the methods comprising polymerizing albumin by crosslinking inter- and intra-molecular disulfide bridges, and PEGylating the albumin polymer. The present invention further provides a pharmaceutical composition useful as a blood plasma expander, blood substitute or for drug delivery, and methods of treating blood loss in a subject and of delivering drugs to a subject's tissue, the pharmaceutical composition comprising a therapeutically effective amount of the PEGylated albumin polymer.

Abstract: The invention relates to variants of albumin. The invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of preparing the variants and to methods of using the variants.

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Abstract: The invention is directed to biodegradable, thermoplastic, phase separated segmented multi-block copolymers. The copolymers of the present invention find use in various biomedical applications as well as in pharmaceutical applications. Provided is a composition for the controlled release of at least one biologically active polypeptide to a host, comprising the at least one biologically active polypeptide encapsulated in a matrix comprising at least one phase separated, thermoplastic multi-block copolymer, the copolymer being characterized in that (i) it comprises at least two hydrolysable segments chosen from prepolymer (A) and prepolymer (B), prepolymer (A) having a Tg lower than 37° C. and prepolymer (B) having a Tm of 40° C.-100° C. under physiological conditions; (ii) the segments being linked by a multifunctional chain-extender; (iii) the segments are randomly distributed over the polymer chain; and (iv) prepolymer (A) contains a segment that is derived from a water soluble polymer.

Abstract: The present invention provides a novel nanoparticle drug delivery system generated from poly(ortho ester) polymers with sustained drug release capability and can be functionalized to allow for systemic delivery to various organ systems throughout the body. One important aspect of this invention is that the nanoparticle drug delivery system generated from poly(ortho ester) polymers encapsulate several types of drugs in poly(ortho ester) nanoparticles, including but not limited to lipophilic, hydrophilic small and large molecules and also hydrophilic and lipophilic dyes by adopting appropriate emulsion techniques. These poly(ortho ester) nanoparticles are biodegradable, biocompatible and controlled release drug delivery system with zero order kinetics, which can be used in various biomedical applications such as eye-related diseases, cancer, arthritis, etc.

Abstract: Provided herein are phenylboronate containing co-polymers (PCC), compositions containing PCC and polyvinyl alcohol (PVA), such compositions further including proteins, methods of making these compositions by water in oil polymerization, and methods of using the protein containing compositions for releasing proteins. Such phenylboronate containing co-polymers are of Formula I: where m, n, p, x, R1-R5, L, X1 and X2 are defined in the application.