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MarketScreener Homepage  >  Equities  >  Tokyo  >  Sysmex Corp    6869   JP3351100007

SYSMEX CORP (6869)
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Sysmex : Researchers Submit Patent Application, "Method for Controlling Affinity of Antibody for Antigen, Antibody Whose Affinity for Antigen Has Been...

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07/12/2018 | 11:58pm CEST

Researchers Submit Patent Application, "Method for Controlling Affinity of Antibody for Antigen, Antibody Whose Affinity for Antigen Has Been Altered, and Its Production Method", for Approval (USPTO 20180179298)

By a News Reporter-Staff News Editor at Life Science Weekly -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors MAETA, Shingo (Kobe, JP); FUKUNAGA, Atsushi (Kobe, JP), filed on December 27, 2017, was made available online on July 5, 2018 (see also Sysmex Corporation).

The patent's assignee is Sysmex Corporation.

News editors obtained the following quote from the background information supplied by the inventors: "Conventionally, a technique for altering affinity of an antibody for an antigen by introducing a mutation into the amino acid sequence of the antibody has been known. For example, US 2012/0329995 A describes a method of introducing a mutation into the amino acid sequence of complementarity determining region (CDR) of an antibody to reduce the affinity of the antibody for an antigen.

"It has been also known to alter affinity for an antigen by introducing a mutation into the amino acid sequence of the framework region in a variable region not into that of CDR. For example, Fukunaga A and Tsumoto K, Improving the affinity of an antibody for its antigen via long-range electrostatic interactions, Protein Eng. Des. Sel. Vol. 26, no. 12, p. 773-780, 2013 and WO 2013/084371 A describe that the 60th, 63rd, 65th and 67th amino acid residues located in the framework region 3 of the single chain antibody (scFv) binding to troponin I are substituted with a basic amino acid lysine or arginine residue. Troponin I is an antigen with a high content of charged amino acids. In Fukunaga A and Tsumoto K, Improving the affinity of an antibody for its antigen via long-range electrostatic interactions, Protein Eng. Des. Sel. Vol. 26, no. 12, p. 773-780, 2013 and WO 2013/084371 A, firstly, a single chain antibody recognizing an acidic epitope with a pI of 3.57 and a single chain antibody recognizing a basic epitope with a pI of 11.45 are prepared. Fukunaga A and Tsumoto K, Improving the affinity of an antibody for its antigen via long-range electrostatic interactions, Protein Eng. Des. Sel. Vol. 26, no. 12, p. 773-780, 2013 and WO 2013/084371 A describe that the affinity to troponin I could be improved by utilizing the electrical attraction generated by the introduction of basic amino acid residues into these single chain antibodies."

As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors' summary information for this patent application: "The scope of the present invention is defined solely by the appended claims, and is not affected to any degree by the statements within this summary.

"In Fukunaga A and Tsumoto K, Improving the affinity of an antibody for its antigen via long-range electrostatic interactions, Protein Eng. Des. Sel. Vol. 26, no. 12, p. 773-780, 2013 and WO 2013/084371 A, from the viewpoint of increasing the binding rate constant in the antigen-antibody reaction, the mutation as described above is introduced in the framework region 3 (FR3) of the anti-troponin I antibody to improve the affinity for troponin I. However, these literatures do not describe whether antibodies other than anti-troponin I antibody can alter affinity for an antigen by the same method.

"Also, Fukunaga A and Tsumoto K, Improving the affinity of an antibody for its antigen via long-range electrostatic interactions, Protein Eng. Des. Sel. Vol. 26, no. 12, p. 773-780, 2013 and WO 2013/084371 A describe only that the affinity for an antigen has been improved. On the other hand, when using an antibody as a reagent, not only an antibody with improved affinity for an antigen but also an antibody with reduced affinity may be required. For example, an antibody with reduced affinity for an antigen can be used as an appropriate control for antigen-antibody reactions. Therefore, establishment of a technique for controlling affinity of an antibody for an antigen is desired.

"The present inventors have found that, by substituting the amino acid residue of FR3 of an antibody with a charged amino acid residue, the affinity for an antigen can be improved or reduced depending on the type of the antibody. Then, the present inventors have found that such difference in affinity change is related to the electrical characteristic of CDR determined based on the number of charged amino acid residues contained in the CDR, thereby completing the present invention.

"Thus, a first aspect of the present invention provides a method for controlling affinity of an antibody for an antigen. In this method, in an antibody whose electrical characteristic of CDR based on the amino acid sequence of the CDR is neutral or negatively charged, at least 3 amino acid residues of FR3 defined by the Chothia method are substituted with charged amino acid residues.

"Also, a second aspect of the present invention provides a method for producing an antibody whose affinity for an antigen has been altered. This method comprises the steps of substituting at least 3 amino acid residues of FR3 defined by the Chothia method with a charged amino acid residue in an antibody whose electrical characteristic of CDR based on the amino acid sequence of the CDR is neutral or negatively charged, and recovering the antibody obtained in the substitution step.

"Furthermore, a third aspect of the present invention provides an antibody whose affinity for an antigen has been altered. In this antibody, the electrical characteristic of CDR based on the amino acid sequence of the CDR is neutral or negatively charged, and at least 3 amino acid residues of FR3 defined by the Chothia method in the unmodified antibody are substituted with charged amino acid residues."

For additional information on this patent application, see: MAETA, Shingo; FUKUNAGA, Atsushi. Method for Controlling Affinity of Antibody for Antigen, Antibody Whose Affinity for Antigen Has Been Altered, and Its Production Method. Filed December 27, 2017 and posted July 5, 2018. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220180179298%22.PGNR.&OS=DN/20180179298&RS=DN/20180179298

Keywords for this news article include: Antigen T-Cell Receptors, Business, Genetics, Peptides, Immunology, Troponin I, Amino Acids, Biopolymers, Blood Proteins, Immunoproteins, Muscle Proteins, Membrane Proteins, Sysmex Corporation, Contractile Proteins, Cytoskeletal Proteins, Microfilament Proteins, Single-Chain Antibodies, Immunoglobulin Fragments.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2018, NewsRx LLC

(c) 2018 NewsRx LLC, source Health Newsletters

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