摘要:
Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.
摘要:
The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
摘要:
Polypeptides that are cleared from the kidney and do not contain in their original form a Fc region of an IgG are altered so as to comprise a salvage receptor binding epitope of an Fc region of an IgG and thereby have increased circulatory half-life. Methods are described herein which utilize these polypeptides in treating disorders involving the LFA-1 receptor. In one of the described methods of treatment, the polypeptide includes the amino acid sequence PKNSSMISNTP (SEQ ID NO:3) and may also include the sequence selected from the group consisting of HQNLSDGK (SEQ ID NO: 1), HQNISDGK (SEQ ID NO:2), HQSLGTQ (SEQ ID NO:11) and VISSHLGQ (SEQ ID NO:31).
摘要翻译:从肾脏中清除并且不以其原始形式含有IgG的Fc区的多肽被改变,以便包含IgG的Fc区的补救受体结合表位,从而具有增加的循环半衰期。 本文描述了利用这些多肽来治疗涉及LFA-1受体的疾病的方法。 在所述治疗方法之一中,多肽包括氨基酸序列PKNSSMISNTP(SEQ ID NO:3),并且还可以包括选自HQNLSDGK(SEQ ID NO:1),HQNISDGK(SEQ ID NO: :2),HQSLGTQ(SEQ ID NO:11)和VISSHLGQ(SEQ ID NO:31)。
摘要:
A fibrinolytically active amino acid sequence variant of a plasminogen activator is prepared that has one or more glycosylation sites in regions that are not glycosylated in the native molecule. DNA sequences can be prepared that encode the variants, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The variants may be used in a pharmaceutical preparation to treat a vascular disease or condition in patients.
摘要:
A tissue plasminogen activator (t-PA) variant is prepared that has an amino acid deletion at positions 466 to 470 of the corresponding wild-type t-PA. This alteration renders the variant fibrin (and plasma clot) specific as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the variant, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The variant may be used in a pharmaceutical preparation to treat a vascular disease or condition or to prevent fibrin deposition or adhesin formation or reformation in mammals.
摘要:
The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.
摘要:
The invention relates to binding compounds that specifically bind to human TSLP, as well as uses thereof, e.g., in the treatment of inflammatory disorders and allergic inflammatory response.
摘要:
The present invention provides, in part, MCP1-Ig fusion polypeptides exhibiting surprisingly beneficial properties as well as methods for treating various diseases (e.g., inflammatory diseases) by administering any of such fusions.
摘要:
The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins, heteromultimers and antibody-immunoadhesin chimeras. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.