National Cheng-Kung University

National Taiwan University

Dcb-usa LLC

Woei-Jer Chuang

Wen-Mei Fu

Tur-Fu Huang

Yen-Lun Huang

Mannching Sherry Ku

Wenya Huang

Chih-Hsin Tang

Yung-Sheng Chang

Chiu-Yueh Chen

Yu-Ju Kuo

The present invention provides a protein, and the protein includes a 10th human fibronectin type III domain and has a first mutation at an amino acid residue with a cysteine residue and a second mutation at another amino acid residue with another cysteine residue, wherein the first mutation and the second mutation take place at a region of the 10th human fibronectin type III domain other than a loop FG so that a disulfide bond is formed between the cysteine residue formed by the first mutation and the cysteine residue formed by the second mutation.

Fibronectin type III domain-based protein and application thereof

Disclosed herein are disintegrin variants, and methods for suppressing or inhibiting platelet aggregation in a subject in need thereof. The method includes administering to the subject in need thereof an effective amount of the present disintegrin variant to alleviate or ameliorate symptoms associated with diseases, disorders, and/or conditions resulted from platelet aggregation. According to preferred embodiments, the present disintegrin variant is applied as a coating on an implantable device, such as a stent or a catheter.

Disintegrin variants and uses thereof

Disintegrin variants that bind specifically to one or more of &#x3b1;5&#x3b2;1 and &#x3b1;v integrins, such as &#x3b1;v&#x3b2;1, &#x3b1;v&#x3b2;3, &#x3b1;v&#x3b2;5, &#x3b1;v&#x3b2;6 and &#x3b1;v&#x3b2;8, but with reduced binding activity to &#x3b1;IIb&#x3b2;3, are described. Also described are uses of the disintegrin variants for the treatment or prevention of a disease associated with an &#x3b1;v integrin or an &#x3b1;5&#x3b2;1 integrin.

Disintegrin variants and pharmaceutical uses thereof

The present invention provides isolated polypeptides comprising a modified fibronectin fragment that comprises FNIII 10 and optionally further comprising FNIII 9. Also provided are pharmaceutical compositions comprising the polypeptides and methods of making and using the polypeptides.

Modified fibronectin fragments or variants and uses thereof

The invention generally relates to compositions and methods of treatment and/or prevention of angiogenesis-related eye diseases using low doses of rhodostomin variants, and in particular, low doses of a fusion protein comprising a rhodostomin variant, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA) where the cysteine residue at position 34 of the HSA amino acid sequence has been replaced with serine.

Compositions and methods for the treatment of angiogenesis-related eye diseases

The invention provides disintegrin variants, and more specifically to disintegrin variants which are selective &#x3b1;v&#x3b2;3 integrin antagonists for treatment and prevention of &#x3b1;v&#x3b2;3 integrin-associated diseases. The present invention also relates to pegylated proteins, including proteins comprising a disintegrin variant having an RGD motif variantARLDDL. The invention also relates to the use of the polypeptides of the invention for the treatment and prevention of &#x3b1;v&#x3b2;3 integrin-associated diseases.

Methods of treating &#x3b1;v&#x3b2;3 integrin-associated diseases by administering polypeptides selective for &#x3b1;v&#x3b2;3 integrin

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin &#x3b1;v&#x3b2;3 receptor-antagonist activity and substantially reduced integrin &#x3b1;llb&#x3b2;3 and/or &#x3b1;5&#x3b2;1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin &#x3b1;llb&#x3b2;3 and/or &#x3b1;5&#x3b2;1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of &#x3b1;v&#x3b2;3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.

Growing community of inventors

Tainan, Taiwan

Woei-Jer Chuang