DETAILED ACTION
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 .
Claim Status
Claims 1-18 were pending in the present application. By virtue of a Preliminary Amendment, filed by Applicant on 21 September 2022, claims 7-10 and 16-18 were amended. Therefore, claims 1-18 remain pending and are currently under examination.
Priority
This application is a national stage 371 application of PCT/JP2021/011753 filed 22 March 2021. This application claims foreign priority of JP2020-051139 filed 23 March 2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386 (c) is acknowledged. Receipt of certified copies of papers required by 37 CFR 1.55 is acknowledged. However, the foreign priority document received on 21 September 2022 is not in English, and therefore, the examiner cannot ascertain whether said document discloses the invention for purposes of priority. Consequently, the effective filing date for applying prior art is 22 March 2021 (the date PCT/JP2021/011753 was filed).
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Accordingly, the filing date of the PCT/JP2021/011753 application, filed on 22 March 2021, will be used for the purpose of applying prior art.
Information Disclosure Statement (IDS)
The IDSs (2) filed on 28 October 2022 and 17 April 2024 have been considered by the examiner. Signed copies are enclosed.
Applicant is reminded of their duty to disclose to the Office all information known to the
person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach
individual associated with the filing and prosecution of a patent application has a duty of candor
and good faith in dealing with the Office, which includes a duty to disclose to the Office all
information known to that individual to be material to patentability as defined in this section.”
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon judicial exception without significantly more. Claim 1 recites a method which, in its broadest reasonable interpretation, is drawn to naturally occurring phenomenon. The claims do not integrate the naturally occurring phenomenon into a practical application because they do not recite any additional steps, structures, or elements apart from the naturally occurring phenomenon.
Claim 1 is drawn to a method to produce trimeric and tetrameric IgA antibodies comprising mixing a dimeric IgA antibody and a monomeric IgA antibody. Claim 2 is drawn to the method of claim 1 that further comprises mixing a secretory component with the dimeric IgA antibody and monomeric IgA antibody. Applicant’s disclosure references ‘mixing’ multiple times, specifically the mixing occurs in vitro a dimeric antibody and monomeric IgA antibody each prepared in separate cultured cells (Specification p. 3, lines 11-16). However, Applicant’s disclosure further states that “a bispecific trimeric or tetrameric antibody is produced by a simple method comprising only mixing in vitro at least two types of proteins: a dimeric IgA antibody and a monomeric IgA antibody” (Specification p. 7, lines 20-23).
Currently claimed 1 and 2 do not indicate any changes or additional elements apart from mixing of a monomeric IgA antibody, a dimeric IgA antibody, and a secretory component. The mixing of a monomeric IgA antibody and dimeric IgA antibody is described in the art as a naturally occurring phenomenon as evidenced by Patel: “plasma cells in the mucosal subepithelium secrete monomeric IgA, which then complexes by covalent bondage through J chains to form dimeric IgA” (p. 2).1 Patel provides evidence that, at some point in time, the monomeric IgA antibodies secreted by the mucosal subepithelium come into contact with an already-formed dimeric IgA antibody, which is then released with a secretory component derived from a polymeric Ig receptor (p. 2).2 Furthermore, Saito states the following: “monomeric, dimeric, tetrameric IgA are found to be included at various ratios in sera from patients with multiple myeloma” ([0006]).3 Therefore, and without any evidence to the contrary, the method of claim 1 and dependent claim 2 would not be markedly different than the naturally occurring phenomenon and the claimed invention does not have markedly different characteristics from what exists in nature. See, e.g., MPEP 2106, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013); Roche Molecular System, Inc. v. CEPHEID, 905 F.3d 1363, 1371, 128 USPQ2d 1221, 1227 (Fed. Cir. 2018).
Accordingly, the claims are directed to a judicial exception. Because claims 1 and 2 do not recite any additional steps, elements, or structures that could add significantly more to the exception, the claims do not qualify as eligible subject matter under 35 U.S.C §101.
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.
Claims 1, 2, 7, 10, and 11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Saito (US 2017/0340732; published: 30 November 2017).
Saito discloses polymeric IgA-type recombinant antibodies and methods of producing this antibody (abstract, [0147]).
Regarding instant claim 1, Saito discloses a polymeric IgA-type recombinant antibody is a mixture of monomeric, dimeric, trimeric, and tetrameric antibodies ([0106]). Experimental Example 4 described the production of a polymeric IgA1-type antibody ([0224]-[0236]) and Experimental Example 21 provides data for the mass spectrometer analysis of this antibody ([0355]-[0364]). Data shows the tetrameric IgAm2 contains a mixture of monomers and dimers ([0361]-[0362], Table 8).
Regarding instant claim 2, Saito discloses the addition of a secretory component to the mixture to produce the antibodies in Experimental Example 4 ([0225]).
Regarding instant claim 7, Saito discloses the secretory component is mutated (p. 35, SEQ ID NO: 31).
Regarding instant claims 10 and 11, Saito discloses the IgA1 and IgA2 antibodies were separated based on molecular size using size exclusion chromatography ([0283]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3-4, 12-13, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Saito (previously cited) in further view of Keyt (US 2016/0368971; published: 22 December 2016).
The disclosures in Saito are discussed above. Though Saito does not explicitly disclose the limitations of instant claims 3-4, 12-13, and 17-18, these components of the currently claimed invention are made obvious in view of Keyt.
Keyt discloses IgA multi-specific binding molecules, methods for their preparation, and use (abstract). In addition, Keyt discloses bi- and multi-specific IgA antibodies have great potential in the treatment of respiratory virus infections, various bacterial infections of the gastrointestinal tract, and immunology of cancer ([0010]).
Regarding instant claims 3 and 12, Keyt discloses the methods of the present invention will result in a composition comprising a bispecific IgA antibody possibly in combination with monomers, dimers, trimers, and/or tetramers of the bispecific binding unit ([0128]). Furthermore, Keyt discloses that in some embodiments of the bispecific binding molecule, each of the binding units is monospecific (AA, BB), each binding to a different binding target (A and B, respectively) ([0012]). Keyt further discloses the bi-specific antibody of the invention has at least two antigen-binding sites ([0007]).
Regarding instant claim 4, Keyt discloses that in some embodiments of the bispecific binding molecule, each binding unit is bispecific with different binding specificities ([0104]).
Regarding instant claim 13, Keyt discloses the bi-specific antibody can further comprise a secretory component ([0054], [0059]).
Regarding instant claim 17, Keyt discloses the bi-specific antibody can further comprise a secretory component ([0054], [0059]). While Keyt does not explicitly disclose the secretory component can be a wild type or mutant, Saito identifies the secretory component by sequence identifier and indicates the secretory component suitable for use with polymeric IgA antibodies can be a mutant secretory component (p. 35, SEQ ID NO: 31).
Regarding instant claim 18, Keyt discloses the bi-specific antibody can be formulated into a pharmaceutical composition ([0155]-[0157]).
A combination of Saito and Keyt disclose the limitations of instant claims 3-4, 12-13, and 17-18. Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the combined teachings of the references to arrive at the claimed invention. Both Keyt and Saito disclose a method of making IgA antibodies. Keyt further discloses a method of making bi-specific IgA antibodies and their potential in the treatment of respiratory virus infections, various bacterial infections of the gastrointestinal tract, and immunology of cancer ([0010]). Keyt not only discloses the limitations of instant claims 3-4, 12-13, and 17-18, but also provides motivation to manipulate the base IgA antibody taught by Saito to include bi-specific properties and antigen-binding configurations. Therefore, one of ordinary skill in the art could improve upon the base method and composition disclosed by Saito with what is taught in Keyt and arrive at what is currently claimed in instant claims 3-4, 12-13, and 17-18 with reasonable expectation of success.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Saito (previously cited) in further view of Lilie (“Influence of protein disulfide isomerase (PDI) on antibody folding in vitro,” published: 13 May 1994).
The disclosures in Saito are discussed above. Though Saito does not explicitly disclose use of a molecular chaperone protein, a disulfide bond isomerase, oxidized glutathione, and reduced glutathione as required by instant claim 8, these components of the currently claimed invention are made obvious in view of Lilie.
Lilie teaches eukaryotic protein disulfide isomerase (PDI) is known to participate in the disulfide bond formation of immunoglobulins in vivo (abstract). Lilie further teaches PDI catalyzes the assembly of IgM and IgA in vitro (p. 14290). Finally, Lilie teaches PDI influences the yield of reactivation enormously and in the presence of PDI, formation of the correct disulfide bonds is possible at higher oxidizing conditions compared to the spontaneous reaction (abstract). Therefore, Lilie teaches the necessity of PDI in antibody formation especially in the early phases of structure formation (p. 14296).
A combination of Saito and Lilie disclose the limitations of instant claim 8. Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the combined teachings of the references to arrive at the claimed invention. Saito discloses a method of making an IgA antibody while Lilie, which was published in 1994, teaches a technique using protein disulfide isomerase during antibody formation is well-known in the art to play a role in facilitating antibody formation particularly in the early phases of structural formation. Therefore, one of ordinary skill in the art could improve upon the base method disclosed by Saito with what is taught in Lilie as a wildly known and beneficial addition to antibody formation to arrive at what is currently claimed in instant claim 8 with reasonable expectation of success.
Claim Objections
Claims 5-6. 9, and 14-16 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Prior art, including the references Saito and Keyt, do not explicitly disclose which component (monomer or dimer) of the trimeric or tetrameric antibody contains which antigen binding site nor does either reference contain motivation for this limitation. Furthermore, neither reference explicitly teaches separately producing the recombinant dimeric and monomeric IgA antibody in separate cells. In fact, Saito teaches against this limitation as the scope of Saito’s invention involves producing antibodies in a single cell, rather than multiple and different cells (see, for example, abstract and [0134]: “the present inventors have first succeeded in unexpectedly producing a polymeric IgA-type antibody by coexpressing a secretory component protein in a single cell together with an IgA-type antibody heavy-chain protein, an antibody light-chain protein, and an antibody J-chain protein”).
Conclusion
Claims 1-4, 7-8, 10-13, and 17-18 are rejected. Claims 5, 6, 9, and 14-16 are objected to. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-F 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIA A ROSSI/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
1 Patel A, Jialal I. “Biochemistry, Immunoglobulin A.” Available from: https://www.ncbi.nlm.nih.gov/books/NBK551516/
2 Id.
3 Saito et al. US 2017/0340732. Published: 30 November 2017.