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 .
Status of Claims
Claims 1-6, 16, 23-25, 28-31 and 37-41 are currently pending. Claims 23-25 are allowed.
Comments regarding Applicants allegations of discussion provided in the interview held October 22, 2025:
Applicant alleges “examiner asserted these differences [of structural features from expression in insect cells compared to mammalian cells] would need to be shown experimentally for this to carry weight.” (Remarks pg. 9;emphasis added). Examiner clarifies that it was merely suggested objective evidence as to the facts regarding structural differences could be effective way to overcome a prima facie case of anticipation of a product-by-process limitation. Examiner asserts herein that objective evidence would be needed to support such allegations of structural differences particularly in the case where expression in insect cells results in the functional capacity to bind autoantibodies and expression in some mammalian cells fails to do so (Callaghan in the Abstract regarding expression in COS cells).
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 1-4, 6, 28, and 37-40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma et al. Scandinavian J Gastroenterol. 1994. 29(9):790-794, as cited in the IDS filed January 30, 2020; as evidenced by UniProt. P51164 · ATP4B_HUMAN. History. November 7, 2018. Retrieved from the Internet at <URL: https://www.uniprot.org/uniprotkb/P51164/history>.
Applicant's arguments filed November 3, 2025 have been fully considered but they are not persuasive.
Examiner maintains that thus far on the record Applicants have only made assertions without providing objective evidence or arguments other than merely alleging that it is “well-known” that expression in insect cells can result in structural differences from post-translational modification compared to expression in mammalian cells (see, e.g., Remarks on pg. 10 in the last ¶ spanning pg. 11).
MPEP 2145 I states:
“An argument by the applicant is not evidence… Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case[.]").”
In contrast to Examiner’s reasoned interpretation of the claim limitation supported by objective evidence on the record (see Office Action mailed August 7, 2025 on pg. 3 in the last ¶ spanning pg. 4), Applicant has provided no objective evidence regarding the alleged structural difference of proteins expressed by insect cells compared to mammalian cells.
Consider the following:
“The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)” (cited from MPEP 2113 I.)
The evidence of record indicates that one of ordinary skill would expect that expression in a mammalian cell imparts structural characteristics that can either result in autoantibody binding (Lahner; see the last full ¶ of the first col. on pg. 3 regarding expression in Expi293F cells) or fail to result in autoantibody binding (Callaghan in the Abstract regarding expression in COS cells). Where the claims are directed to a process for capturing autoantibodies against the beta-subunit of H+/K+-ATPase, it is meaningless to interpret the limitation of “an agent that is only provided from… a mammalian cell” as encompassing structures of said agent that fail to bind said autoantibodies. Examiner maintains that the structure implied to the person having ordinary skill in the art by “said agent is only provided from… a mammalian cell” given the broadest reasonable interpretation in the context of the claimed invention is an amino acid sequence with post-translational modification sufficient to bind an autoantibody. The expression in insect cells as taught by Ma satisfies this interpretation and Applicant has not sufficiently provided facts supported by objective evidence to persuasively overcome the prima facie case of anticipation. For example, Applicant has not pointed out what particular structure is produced by post-translational modification in mammalian cells that allegedly distinguishes the product from that which is produced from insect cells.
Where Applicant alleges that the amendment to claim 1 distinguishes the claimed invention over Ma because Ma previously analyzed samples for binding to the alpha-subunit (see Remarks on pg. 11 in the first full ¶), Examiner respectfully points out that 14 of the samples which Ma detected binding to the beta-subunit also had no detected binding to the alpha subunit (Ma in the last ¶ on pg. 794 spanning pg. 795). Therefore, it would be apparent to the skilled artisan that Ma teaches 14 samples “wherein an autoantibody against the alpha-subunit is not detected in the sample at any point in time or on the same carrier [as the beta subunit].” Note well, where the amendment recites “at any point in time or on the same carrier,” “at any point in time” and “on the same carrier” are interpreted as alternative limitations.
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.
5. Claims 1-6, 28-31, and 37-40 stand rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. Scandinavian J Gastroenterol. 1994. 29(9):790-794; as applied to claims 1-4, 6, 28, and 37-40 and further in view of Robinson et al. in US 20030003516 A1 published on January 2, 2003; as evidenced by Toh. Autoimmunity Reviews. 2014. 13:459-462, cited herewith and UniProt. P51164 · ATP4B_HUMAN. History. November 7, 2018. Retrieved from the Internet at <URL: https://www.uniprot.org/uniprotkb/P51164/history>.
6. Claim 1, 2, 4, 6, 16, 30, 31, 37, 39, 41 stand rejected under 35 U.S.C. 103 as being unpatentable over Callaghan et al. Autoimmunity. 1993. 16:289-295 in view of Ma et al. Scandinavian J Gastroenterol. 1994. 29(9):790-794; as evidenced by UniProt. P51164 · ATP4B_HUMAN. History. November 7, 2018. Retrieved from the Internet at <URL: https://www.uniprot.org/uniprotkb/P51164/history>.
Applicant's arguments filed November 3, 2025 have been fully considered but they are not persuasive.
Again, Applicant repeats the allegation that it is “well known” that post-translational modifications in insect cells result in different structures from those in mammalian cells. Noted herein:
“‘The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).”
Applicant has provided no objective evidence establishing a nonobvious difference between the agent used in the instant claims and the agent produced by the method of Ma. Moreover, considering the ordinary level of skill in the art for expressing recombinant protein in mammalian cells, e.g. as evidenced by Robinson’s teaching that “[m]any strong promoters for mammalian cells are known in the art” in ¶ [107] on pg. 12, using the structure of an agent produced by a mammalian cell in the method disclosed by Ma in view of Robinson would have been prima facie obvious.
Applicant alleges that the amendment to claim, regardless, distinguishes the claimed invention over Ma (see the second full ¶ on pg. 12). For the reasons indicated above, Examiner respectfully disagrees. Moreover, even if this were not the case, the argument is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Robinson teaches the beta-subunit and intrinsic factor and is silent with respect to the alpha-subunit. In the absence of evidence to the contrary, Robinson teaches a method which does not detect the alpha-subunit at any point in time.
Applicant alleges that “nothing in Robinson indicates that [the combination of Ma with Robinson] would be beneficial compared to using the complete ATPase as already shown in Ma.” (see pg. 12 in the last full ¶). However, the scope of the instant claim does not exclude using the complete ATPase, rather it limits the claimed method to one in which autoantibodies against the alpha-subunit is “not detected” in the sample at any point in time or on the same carrier, which Ma evidences as being obvious for a subset of samples.
Applicant argues that the instant specification does speak to specificity (pg. 12 in the last ¶ spanning pg. 13). While the argument is acknowledged, is unclear without further argument or reasoning how this fact rebuts the prima facie case of obviousness. For all the reasons already stated in the Office Action mailed August 7, 2025, in the last ¶ on pg. 13 spanning pg. 14, the experimental evidence does not show unexpected or surprising properties in view of the prior art.
Applicant argues “Examiner alleges that Driel is not relevant”, “CD4+ T cells are required for B cell selection and proliferation”, and “Driel, Ma and Lahner show… that using ATPase provides better result than using on of its subunits alone.” (Remarks pg. 13 in the first full ¶). The first statement is not factually true. The Office action on pg. 13 states “[w]hile Applicant cites Driel as teaching CD4+ T cell mediated autoimmunity against both subunits, Id. the instant claims and applied art are directed to autoantibodies and not T-cell mediated reactions.” This does not mean that Examiner’s position is “CD4+ T cells are irrelevant to the generation of autoantibodies,” rather that Applicant’s arguments regarding CD4+ T cells do not persuasively overcome the prima facie case in view of the prior art applied which teach autoantibodies. Regardless, the argument is ineffective at overcoming the prima facie case because, as previously pointed out, the instant claims do not exclude using whole ATPase to test for autoantibodies and, of the three references Applicant cites, only Ma was cited in the rejection.
Applicant argues that “Lahner provides a strong motivation to the skilled person to use both subunits.” (see pg. 13 in the last full ¶). However, Lahner was not cited in the prima facie case of obvious, rather Lahner shows that the instantly claimed method does not result in sensitivity that would be unexpected or surprising to the ordinarily skilled artisan. Insofar as Applicant may allege unexpected properties or surprising results (see Remarks pg. 13-14), the instantly claimed method does not exclude using whole ATPase and is not commensurate in scope with Applicants allegations of surprising results. Moreover, teachings found in the prior art not applied showing a desirable alternative for diagnosis, e.g. in addition to Robinson’s teachings which only explicitly teaches the beta subunit and intrinsic factor, do not persuasively overcome a prima facie case of obviousness. Particularly, no art teaches away from Robinson’s teachings on a multiantigen array using beta-subunit + intrinsic factor. The fact that there are multiple methods in the prior art do not make Robinson’s teachings on beta subunit + intrinsic factor any less obvious to use.
In conclusion, when Applicant’s arguments are taken as a whole and weighed against the evidence supporting the prima facie case of unpatentability, the instant claims, by a preponderance of evidence, remain unpatentable. See M.P.E.P. § 716.01(d).
Allowable Subject Matter
7. Claims 23-25 are allowed.
8. Allowable subject matter has been noted (see attached Email communication). Specifically, the Examiner proposed amendments uses language directly recited in the specification at pg. 10 in lines 21-29. The Examiner proposed amendments clearly distinguishes the claimed invention over Robinson’s multiantigen array comprising a panel comprising the beta subunit of H+/K+-ATPase and intrinsic factor because where Robinson is directed to multiantigen arrays in which “[s]mall amounts of the sample are sufficient to screen a large number of different peptides[,]” (pg. 4 in ¶ [0025]) it would not have been obvious to the skilled artisan to only screen for autoantibodies against the beta subunit of H+/K+-ATPase within a sample of a subject. Note well, “a sample” and “the sample” are interpreted with the scope of a singular sample, there being no clear redefinition or disavowal of the scope of “a” and “the” in the instant specification (see MPEP 2111). While the scope of the Examiner proposed amendment does not exclude, e.g., testing for additional biomarkers in additional samples collected from the subject, there would have been no suggestion or motivation in view of the prior art and level of ordinary skill to only test for the beta-subunit of H+/K+-ATPase in a single sample.
Reasons why Applicant’s first counterproposal fail to sufficiently distinguish the claimed invention over the prior art of record, particularly Robinson, were provided in the telephonic interview (see Interview Agenda). Applicant’s most recent counterproposal is:
“Claim 1 would be amended in the last para. to read as follows:
‘wherein the autoantibody against the beta-subunit of gastric H+/K+-ATPase is the sole biomarker tested for in the sample and the sole biomarker captured on the carrier, wherein biomarkers other than gastric H+/K+-ATPase-related biomarkers can be tested for in different samples.’
In addition, if feasible we would like to add a new dependent claim including the wording: ‘wherein the autoantibody against the beta-subunit of gastric H+/K+-ATPase is the sole autoimmune biomarker derived from the gastric H+/K+-ATPase tested for in the sample and the sole autoimmune biomarker derived from the gastric H+/K+-ATPase captured on the carrier.’” (see attached Email communication).
The proposed amendments do not place the application in condition for allowance for the following reasons:
Reciting the beta subunit H+/K+-ATPase as the sole biomarker “captured on the carrier” would create issues of indefiniteness under 35 U.S.C. § 112(b). Lines 2-5 set forth that the agent, the beta subunit H+/K+-ATPase, is immobilized on the carrier and used to capture autoantibodies. In other words, the beta subunit is the bait used to capture autoantibodies. The metes and bounds of further having “captured” the beta subunit on the carrier would be unclear because it contradicts the claim language’s indicated use of the beta subunit.
The limitation “wherein biomarkers other than gastric H+/K+-ATPase-related biomarkers can be tested for in different samples” is not explicitly part of the original disclosure and may be subject to evaluation under 35 U.S.C. § 112(a) for new matter.
The proposed dependent claim has the same issue as the proposed amendment to the independent claim with respect to the use of the term “captured” and may further create issues under 35 U.S.C. § 112(d). The scope of the proposed amendments to claim 1 narrows the scope to only testing for the beta subunit in a sample of a subject. The scope of a limitation wherein the beta subunit is the only H+/K+-ATPase antigen tested for in the sample is necessarily within the scope of the independent claim and may be found to not further limit the scope of the claim from which it depends.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA K SWARTWOUT whose telephone number is (703)756-4672. The examiner can normally be reached Monday-Friday 8-5.
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/B.K.S./Examiner, Art Unit 1644
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683