Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-7) in the reply filed on 9/2/25 is acknowledged. The traversal is on the ground(s) that the two groups do not share a common special technical feature that defines over the prior art. This is not found persuasive because Applicant does not assert a specific reason, but rather states that after Examiner makes a formal rejection based on the prior art cited in the restriction requirement, it will be shown that the two groups indeed share a special technical feature. The restriction is maintained for the reasons set forth in the restriction requirement. Moreover, the grounds for rejection (discussed below) further affirm that the technical feature (of a first binding component that binds to an oxLDL/B2GPI complex, and a second binding component comprising a labeling agent, is not a special technical feature as it does not make a contribution over the prior art in view of Matsuura (US 5,900,359) (see discussion below in the grounds for rejection).
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a written description rejection.
The claims require “a first binding component that binds to an oxLDL/ β2GPI complex” and “a second binding component” that binds to the captured an oxLDL/ β2GPI complex (see claim 1, and repeated recitations in the dependent claims).
Moreover, claim 3 further recites “a first binding unit, which comprises a first specific binding element and the first binding member that specifically binds to the p2GPI molecule comprised in the oxLDL/p2GPI complex, and a second binding unit, which is placed in the predetermined position on the test strip and comprises a second specific binding element that specifically binds to the first specific binding element”.
Also, claim 6 recites: the method as claimed in claim 1, wherein the second binding component comprises a second binding member that specifically binds to an apolipoprotein B-100 (apoB100) comprised in the oxLDL/p2GPI complex.
Additionally, claim 7 recites: the method as claimed in claim 6, wherein binding between the second binding member and the oxLDL/p2GPI complex is based on antigen- antibody binding.
The claims and their dependent claims are rejected for lack of written description regarding the above limitations for the following reasons.
The specification does not describe which amino acid residues, nucleic acid residues or other molecular components are responsible for the functions claimed. Rather, the specification states that these potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. Although the specification provides a few examples of potential generic agents, it fails to disclose the structures common to all members of the genus of peptides encompassed by the broad definition provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of agents that bind to α-syn PFF, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
Regarding the scope of the claims that includes antibodies, the specification does not describe the structure of the full genus of antibodies responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of binding agents (including antibodies) nor guidance as to which of the myriad of molecules encompassed by the binding agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of binding agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, and 5 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 5900359 (hereinafter “Matsuura”).
Applicant’s claim 1 recites: a detection method for detecting a complex of oxidized LDL and β2-glycoprotein I (an oxLDL/ β2GPI complex) in a test sample, which uses a test strip for lateral flow assay, comprising; a step of capturing the oxLDL/ β2GPI complex in the test sample in a predetermined position on the test strip by a first binding component that binds to the oxLDL/ β2GPI complex; and a step of labeling the oxLDL/ β2GPI complex captured in the predetermined position on the test strip by making a second binding component comprising a labeling agent be bound to the captured oxLDL/ β2GPI complex.
Applicant’s claim 2 recites: the method as claimed in claim 1, wherein the first binding component comprises a first binding member that specifically binds to a β2GPI molecule comprised in the oxLDL/p2GPI complex.
Claim 5 recites: the method as claimed in claim 2, wherein binding between the first binding member and the oxLDL/ β2GPI complex is based on antigen-antibody binding.
Matsuura teaches these claimed limitations in the disclosures as follow.
“That is, the present invention relates to a method for determining the complex of β2-GPI and an oxidized lipoprotein (β2-GPI-oxidized lipoprotein complex) by a sandwich assay, using at least two reagents, a solid phase reagent selected from Group A below and an antibody reagent selected from Group B below (Method 1 of the present invention), and to a kit or use in the method (Kit 1 of the present invention):
Group A
(1) an immobilized anti-cardiolipin antibody
(2) an immobilized anti-lipoprotein antibody or an immobilized anti-apolipoprotein antibody
(3) an immobilized anti- β2-GPI antibody
Group B
(1) an anti-cardiolipin antibody
(2) an anti-lipoprotein antibody or an anti-apolipoprotein antibody
(3) an anti- β2-GPI antibody.” Matsuura in col. 2, lines 10-28.
“Anti- β2-GPI is an antibody capable of binding to β2-GPI. Particularly preferred is an antibody that does not recognize a site on β2-GPI to which an oxidized lipoprotein bind.
Anti-cardiolipin antibody
Anti-cardiolipin antibody is an antibody capable of reacting with the complex of phospholipid and β2-GPI, which is observed in serum from patients with autoimmune disease such as anti-phospholipid antibody syndrome.
Anti-lipoprotein antibody
Anti-β2-GPI antibody
Anti- β2-GPI is an antibody capable of binding to β2-GPI. Particularly preferred is an antibody that does not recognize a site on β2-GPI to which an oxidized lipoprotein bind.
Anti-cardiolipin antibody
Anti-cardiolipin antibody is an antibody capable of reacting with the complex of phospholipid and β2-GPI, which is observed in serum from patients with autoimmune disease such as anti-phospholipid antibody syndrome.
Anti-lipoprotein antibody
Anti-lipoprotein antibody is an antibody capable of binding to a lipoprotein. Particularly preferred is an antibody that does not recognize a β2-GPI-binding site on an oxidized lipoprotein.
Anti-apolipoprotein antibody
Anti-apolipoprotein antibody is an antibody capable of binding to an apolipoprotein component in a lipoprotein. Particularly preferred is an antibody that does not recognize a β2-GPI-binding site on an oxidized lipoprotein.” Matsuura in col. 3, lines 16-35.
“A carrier which is employed to prepare the solid phase reagents in Group A as described above may be any conventional carrier. Typical examples of the carrier include a synthetic organic high molecular compound such as polyvinyl chloride, polystyrene, styrene-divinylbenzene copolymer, styrene-maleic anhydride copolymer, nylon, polyvinyl alcohol, polyacrylamide, polyacrylonitrile, polypropylene and polymethylene methacrylate; a polysaccharide such as a dextran derivative (Sephadex, etc.), an agarose gel (Sepharose, Biogel, etc.), a cellulose (paper disk, filter paper, etc.); and an inorganic high molecular compound such as glass, silica gel and silicone. These carriers may be modified by introducing thereon functional groups such as amino, carboxyl, carbonyl, hydroxy and sulfhydryl group. Particularly preferred examples of the carrier are polystyrene and polyvinyl chloride.” Col. 5, lines 5-19.
“The carrier may take any shape such as a flat plate (microtiter plate, disk, etc.), particles (beads, etc.), a tube (a testing tube, etc.), fibers, membrane, fine particles (latex particles, etc.), capsules and vesicles. The shape of the carrier may be appropriately chosen depending on [the] assay method used.” Col. 5, lines 20-25 (emphasis added).
“The solid phase reagents in Group A as described above may be prepared by immobilizing a desired antibody on the carrier. The immobilization of the antibody on the surface of the carrier may be effected by conventional methods such as physical adsorption, ionic binding, covalent binding, and entrapping, as disclosed in Ichiro Chihata, "KOTEIKA KOUSO (Immobilized Enzyme)", published Mar. 20, 1975, Kodansha Publishing Inc. Particularly, physical adsorption is advantageous because of its simplicity. The antibody may be immobilized directly on the surface of the carrier. Alternatively, the antibody may be indirectly immobilized through other substance (a spacer, etc.) on the surface of the carrier.” Col. 5, lines 26-38 (emphasis added).
“The antibody reagent in Group B as described above may also be labeled with a label conventionally employed for an immunoassay. Examples of such a label include a radioisotope (.sup.32 P, .sup.3 H, .sup.14 C, .sup.125 I, etc.); an enzyme (.beta.-galactosidase, peroxidase, alkaline phosphatase, glucose-6-phosphate dehydrogenase, catalase, glucose oxidase, lactate oxidase, alcohol oxidase, monoamine oxidase, etc.); a coenzyme or a prosthetic group (FAD, FMN, ATP, biotin, hem, etc.); a fluorescein derivative (fluorescein isothiocyanate, fluorescein thioflubamyl etc.); a fluorescent dye such as a rhodamine derivative (tetramethylrhodamine B isothiocyanate, etc.), umbelliferone, 1-anilino-8-naphthalenesulfonic acid, and the like; a luminol derivative (luminol, isoluminol, N-(6-aminohexyl)-N-ethylisoluminol, etc.).” Col. 5, lines 43-57 (emphasis added).
“Labeling of the antibody with the label may be carried out by choosing an appropriate method from conventional methods as described in textbooks (e.g., "ZOKU SEIKAGAKU JIKKEN KOZA, 5. MEN-EKI SEIKAGAKU KENKYUHO (Supplemental to Lecture Series on Biochemical Experiment, 5. Study on Immunological Biochemistry)", pages 102-112, 1986, published by Tokyo Kagaku Dojin Publishing Inc.).” Col. 5, lines 58-65 (emphasis added).
“Conventional sandwich immunoassay procedures may be used, in order to determine whether the oxidized lipoprotein is present in a sample using the solid phase reagent and the antibody reagent. That is, the oxidized lipoprotein in a sample can be assayed either by reacting a sample with the solid phase reagent, and further performing B/F separation, if necessary and desired, then reacting with the antibody reagent (a so-called two-step method), or by reacting a sample with the solid phase reagent together with the antibody reagent (a so-called one-step method). In any case, after the reaction has been completed, the oxidized lipoprotein in the sample can be detected or quantitatively determined in a conventional manner.” Col. 5, line 66 to col. 6, line 11.
Thus, regarding Applicant’s claims 1, 2, and 5, Matsuura’s disclosure of materials and methods meets Applicant’s claim 1, wherein the cellulose paper or membrane is equivalent to Applicant’s test strip. The antibody that binds to β2-GPI is equivalent to Applicant’s first binding component that captures the oxLDL/β2GPI complex. The labeled antibody is equivalent to Applicant’s second binding component comprising a labeling agent.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 3 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 5900359 (hereinafter “Matsuura”) in view of US 20100267065 (hereinafter “Geiger”).
Claim 3 recites: the method as claimed in claim 2, wherein the first binding component comprises a first binding unit, which comprises a first specific binding element and the first binding member that specifically binds to the p2GPI molecule comprised in the oxLDL/p2GPI complex, and a second binding unit, which is placed in the predetermined position on the test strip and comprises a second specific binding element that specifically binds to the first specific binding element, and wherein the step of said capturing the oxLDL/p2GPI complex in the test sample in the predetermined position on the test strip comprises, a step of making the oxLDL/p2GPI complex and the first binding member comprised in the first binding unit be bound, and a step of making the first specific binding element of the first binding unit and the second specific binding element of the second binding unit be bound.
Claim 4 recites: the method as claimed in claim 3, wherein the first specific binding element and the second specific binding element are either avidin and biotin or vice versa, streptavidin and biotin or vice versa, or neutravidin and biotin or vice versa, respectively.
Examiner notes that biotin is equivalent to the claimed second specific binding element that is positioned on the test strip. Avidin or streptavidin is equivalent to the claimed first specific binding element to which the second specific binding element (and the antibody discussed above regarding claim 2 is equivalent to the first binding member). Matsuura is silent as to use of biotin and avidin (or streptavidin).
However, Matsuura does teach the following.
“Alternatively, the antibody may be indirectly immobilized through other substance (a spacer, etc.) on the surface of the carrier.” Col. 5, lines 26-38 (emphasis added).
However biotin and avidin binding partners are well known in the art for indirectly immobilizing an antibody to a solid support such as a test strip, as shown by Geiger (see para. 0026).
Geiger discloses the following.
“In addition, those skilled in the art will recognize that antibody a2 may be biotinylated or labeled with some other specific capture label and a specific capture moiety such as a biotin binding protein such as avidin, neutraavidin or streptavidin bound to the test strip enabling both antibodies (a1, a2) to be added to the sample and the entire complex captured, but only antibody a2 captured in a dose responsive manner. Those skilled in the art will recognize that there are many ways to capture antibodies that include but are not limited to His tag, species specific anti-antibodies, Protein A and Protein G in addition to many others. Other potential substrate systems include but are not limited to combining alkaline phosphatase with the commonly known substrate pair BCIP/NBT.”
Thus use of biotin and avidin (or streptavidin) to immobilize the antibody bound to the support in the Matsuura invention would have been obvious to one skilled in the art since such binding partners are well known in the art for binding antibodies on a test strip for performing an assay, as shown by Geiger.
Claim(s) 6 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 5900359 (hereinafter “Matsuura ‘359”) in view of US 20060099644 (hereinafter Matsuura ‘644).
Applicant’s claim 6 recites: the method as claimed in claim 1, wherein the second binding component comprises a second binding member that specifically binds to an apolipoprotein B-100 (apoB100) comprised in the oxLDL/p2GPI complex.
Claim 7 recites: the method as claimed in claim 6, wherein binding between the second binding member and the oxLDL/p2GPI complex is based on antigen- antibody binding.
Regarding claims 6 and 7, Matsuura ‘359 teaches that the second binding component comprises a second binding member (antibody) that specifically binds oxLDL/p2GPI complex (see column 3, lines24-28). However, Matsuura ‘359 does not disclose that the antibody specifically binds to an apolipoprotein B-100 (apoB100) comprised in the oxLDL/p2GPI complex.
Matsuura ‘359 does however teach that the antibody employed can be prepared by known methods (col. 4, lines 49-67). Thus one skilled in the art would have been suggested, with reasonable expectation of success, to utilize known antibodies that meet the disclosed function, such as the antibody disclosed by Matsuura ‘644 (para. 0165, which discloses mouse monoclonal anti-human apoB100 antibody binding to both oxLDL and native LDL and obtained from YAMASA CORPORATION.)
Conclusion
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/Ann Montgomery/ Primary Examiner, Art Unit 1678