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 .
Response to Amendment
Applicant’s response filed 15 September 2025 has been received and entered. Claims 46, 53 and 58 have been amended and claims 1-45 have been previously canceled. Claims 46-58 are currently pending.
Claims 50-52 and 54-56 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02 March 2025.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 15 September 2025 have been fully considered but are not found to be persuasive.
Applicant’s amendment to the claims does not comply with 37 CFR 1.52 (a)(1)(iv-v) which requires that the all papers that are to become a part of the permanent PTO records in the file of a patent application be plainly and legibly written in permanent dark ink or its equivalent and presented in a form having sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of any number of means, including OCR. Claim 58 includes text which is not formed with solid black lines and therefore, appears pixilated and is subject to errors when the text is OCR’d. See below:
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All of the text following “SGLT2 inhibitor” is in a pixilated form. In the next response, a clean set of claims should be submitted in which all the text is presented with solid, black lines which form the text. If a clean set of claims which complies with 37 CFR 1.52 is not provided, the response will be held non-responsive.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09 July 2025 and 15 September 2025 have been considered by the examiner.
Drawings
The drawings were received on 15 September 2025. These drawings are not acceptable.
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1) which requires “India ink, or its equivalent that secures solid black lines”. Several of the Figures do not have solid black lines. See especially Figure 2 in which the lack of solid black lines impacts the clarity of the figure. See sample below:
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Additionally, the font size (see at least Figure 2) is not adequate for clarity purposes and does not appear to meet the requirements of 37 CFR 1.84(p)(3).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Applicant’s substitute specification, filed 15 September 2025, has been received and entered. The submission corrects the previously identified deficiency with the Sequence Rules.
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.
Claim(s) 46-49, 53 and 57-58 is/are rejected under 35 U.S.C. 103 as being unpatentable over Canpolat et al. (cited by Applicant) in view of Zeng et al. (Reg. Toxicol. Pharmacol. 89: 13-19, 2017), Racanelli et al. (Hepatology 43: 554-562, 2006) and Heymann et al. (Nature Reviews: Gastroenterology and Hepatology; 13: 88-110, 2016).
Canpolat et al. (cited by Applicant) teaches an anti-metallothionein antibody which is an inhibitor of metallothionein. Canpolat et al. teaches that endogenous MT synthesized during the normal immune response or as a consequence of toxicant exposure suppresses in vivo immune function (see abstract). Canpolat et al. teach inhibition of metallothionein by administration of an anti-metallothionein antibody and that such inhibition can block the suppression of immune function caused by metallothionein (see page 65, column 2, first paragraph under “Discussion”). The antibody of Canpolat et al. (UC1MT) is the same antibody as disclosed in the instant application. Canpolat et al. does not teach an anti-metallothionein antibody linked to a hepatic cell targeting moiety.
Zeng et al. (Reg. Toxicol. Pharmacol. 89: 13-19, 2017) teach that CSP (circumsporozoite protein) can be used to target a protein of interest to the liver. Zeng et al. teach that targeting a protein to a target tissue can increase its efficacy locally (see page 13, column 2, paragraph 1). Zeng et al. teach the fusion of CSP with a therapeutic protein (interferon) (see page 13, column 2, last sentence).
Racanelli et al. (Hepatology 43: 554-562, 2006) teaches that the liver is an immunological organ and participates in innate and adaptive immunity (see page 560, column 2, final paragraph).
Heymann et al. (Nature Reviews: Gastroenterology and Hepatology; 13: 88-110, 2016) teaches that the liver is a central immunological organ, enriched for innate immune cells (see abstract). Heymann et al. teach that the liver can rapidly activate immunity in response to infections or tissue damage, such as viral hepatitis or NASH.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to attach the hepatic cell targeting moiety of Zeng et al. (CSP) to the anti-metallothionein antibody of Canpolat et al. to obtain a composition which would direct the anti-metallothionein antibody to the liver. Canpolat et al. also teach that metallothionein suppresses immune function and administration of an anti-metallothionein antibody can block the suppression of immune function caused by metallothionein. One would be motivated to attach a hepatic cell targeting moiety to the anti-metallothionein antibody because Racanelli et al. and Heymann et al. teach that the liver is an immunological organ and that the liver can rapidly activate immunity in response to invention and disease and because Canpolat et al. teaches that metallothionein suppresses immunity. It also would have been obvious to one of ordinary skill in the art before the effective filing date to create a fusion protein of an anti-metallothionein antibody and a hepatic cell targeting moiety (CSP) because the prior art of Zeng et al. teach that the targeting moiety is fused to the protein of interest and it was well-known in the art to attach targeting moieties to proteins of interest by expressing the construct as a fusion protein.
Lastly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the composition comprising an anti-metallothionein antibody linked to a hepatic cell targeting moiety (CSP) with a therapeutic agent for treating a condition in need of improving immune function, such as with interferon, because the composition comprising the anti-metallothionein antibody linked to a hepatic cell targeting moiety can be used to block suppression of immune function as taught by Canpolat et al. One would be motivated to make the combination because the antibody targeting moiety composition would block immune suppression and the therapeutic agent would be useful for treating infection in the liver. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Response to Arguments
Applicant argues at page 6 of the response that there is no teaching or suggestion that metallothionein is present extracellularly on liver cells or in the extracellular liver environment and therefore, there is no motivation to make the currently claimed compositions.
Applicant’s argument has been fully considered, but is not found persuasive. The prior art, before the effective filing date of the claimed invention, was aware that metallothionein was present outside of cells, including from the liver (see Lynes et al. – cited on IDS filed 27 October 2023). Applicant’s argument is not persuasive in view of the prior art evidence which was known as of 2006.
Conclusion
No claim is allowed.
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 Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645