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 .
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 13-20 are withdrawn
Claims 1-12 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 2/10/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-16, drawn methods for using a RNF41 nucleic acid.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
Claim 1-12, drawn to a method for using a RNF41 nucleic acid to induce M2-like macrophage morphology.
Claims 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 5/02/2023 and 2/10/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-4, 6-7 and 10-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 3 recites the limitation that the M2-like macrophage morphology consists of “elevated” expression, “elevated” production, or “elevated” collagenase. Claim 4 recites the limitation that the macrophage has “elevated” factors. Claims 10 and 11 recite the limitation that tissue inflammation or fibrosis are “reduced”. Specifically, the term “elevated” and “reduced” are relative terms which renders the claims indefinite (see MPEP 2173.05(b)). The terms "elevated" and “reduced” not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree of elevation relative to other cell types and/or reduction relative to other tissue types. In other words, it is unclear if the elevations in the M2-like macrophages are compared to non-polarized macrophages, and it is equally unclear if the elevations of the macrophage are compared to some other cell type or contacting step. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 6 recites the limitation "the subject" in regard to Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1 does not recite a subject, thereby rendering Claim 6 incomplete. Dependent claims 7, and 10-12 are included in the basis of this rejection because they too are directed to the subject with no proper antecedence.
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 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al., (Nature Immuno, 2009, 10(7):744-754, see IDS filed 5/02/2023).
In regard to claim 1, Wang teaches an in vitro method of inducing a M2-like phenotype in RAW264.7 macrophages by transfection with a polynucleotide encoding RNF41 (alias Nrdp1) (p. 745, Results, 1st para.).
In regard to claim 2, it is well known that the RAW264.7 macrophages were isolated from a murine tumor, and are therefore reasonably considered as tumor-associated macrophages.
In regard to claim 4, Wang teaches the untransfected RAW264.7 macrophages have elevated anti-inflammatory factors (i.e., IFN-beta) in response to LPS compared to RAW264.7 macrophages transfected with a dominant negative Nrpd1 (see Supplemental Fig. 6C). Note as stated above, the scope of the elevation is unclear as to what cells and conditions are being compared.
Accordingly, Wang anticipates instant claims.
Claims 1, and 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ye et al., (JBC, 2012, 297:26740-26748, see IDS filed 5/02/2023).
In regard to claim 1, Ye teaches an in vitro method of inducing a M2-like phenotype in RNF41 transgenic macrophages cultured in IL-4 (p. 26742, Results, last para., see also Fig. 2). Note that Applicant’s “contacting” step is not defined by the specification, and under the broadest reasonable interpretation is being interpreted as encompassing a macrophage with an incorporated RNF41 polynucleotide composition.
In regard to claim 3, Ye teaches the RNF41 transgenic M2-like macrophages are cultured in IL-4 to induce a M2 phenotype, and exhibit increased expression of the mannose receptor (i.e., CD206) relative to non-transgenic/non IL-4 treated macrophages (Fig. 2B). Note as stated above, the scope of the elevation is unclear as to what cells and conditions are being compared.
In regard to claim 4, Ye teaches the non-transgenic (WT) macrophages are cultured in IL-4 to induce a M2 phenotype, and exhibit increased expression of anti-inflammatory factors such as IL-10 relative to non IL-4 treated macrophages (Fig. 2C). Note as stated above, the scope of the elevation is unclear as to what cells and conditions are being compared.
Accordingly, Ye anticipates instant claims.
Claims 1, 3-7, and 10 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Yang et al., (CN1119450576A, filed 7/27/2020, published 10/30/2020).
In regard to claim 1, Yang teaches of contacting macrophages with a NRDP1 (alias RNF41) expression cassette (Abstract, p. 8 of translation, section 2)
In regard to claim 3, Yang teaches the macrophages are cultured in IL-4 to induce a M2 phenotype before NRDP1 transfection to make M2-like macrophages (p. 8 of translation, section 1). Although Yang is silent to increased expression of the mannose receptor CD206 on the IL-4 treated NRDP1 transfected M2-like macrophages, this is an inherent feature of these cells compared to non IL-4 treated/non NRDP1 transfected cells of another type. Note as stated above, the scope of the elevation is unclear as to what cells and conditions are being compared.
In regard to claim 4, Yang teaches the macrophages are cultured in IL-4 to induce a M2 phenotype before NRDP1 transfection (p. 8 of translation, section 1). Furthermore Yang teaches the M2 phenotype induce a Th2-type immune response, produce anti-inflammatory cytokines, and have the ability to promote tissue repair and reconstruction (Abstract, Background, 1st para.). Note as stated above, the scope of the elevation is unclear as to what cells and conditions are being compared.
In regard to claim 5, Yang teaches the RNF41 is delivered as an effective amount for “gene therapy”, and teaches the RNF41 adenoviral gene therapy vector in a 0.9% PBST solution (pgs. 2-3 of translation, see also claim 10 of Yang). Furthermore, Yang teaches transfecting the hematoma surrounding the tissue of a cerebral hemorrhage to effectively inhibit the inflammatory reaction (p. 6, section 13 of translation).
In regard to claim 6, as stated supra, Yang teaches subjects are at risk to tissue injury by cerebral hemorrhage (Abstract, p. 3 of translation, Contents of the Invention).
In regard to claim 7, CNS tissue is well known to be a tissue of the mononuclear phagocyte system.
In regard to claim 10, Yang teaches RNF41 transfected macrophages are effective at inhibiting immune activation after cerebral hemorrhage (p. 3, Contents of the Invention), therefore the CNS tissue inflammation would inherently be reduced. Note as stated above, the scope of the reduction is unclear as to what tissues and conditions are being compared. It is also noted that the "wherein tissue inflammation is reduced” clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. gene therapy with RNF41 to macrophages in CNS tissue). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
Accordingly, Yang anticipates instant claims.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 6-8, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (CN 1119450576A, filed 7/27/2020, published 10/30/2020), in view of Forbes et al., (US 11,285,174, filed 9/18/2017, patented 3/29/2022).
As discussed previously, Yang teaches a gene therapy method of inducing M2-like macrophage morphology in a macrophage comprising contacting a macrophage with a composition comprising a polynucleotide encode RNF41.
However, claim 1 is not limited to a gene therapy method and Yang alternatively teaches that cell therapy methods comprising transfecting macrophages with the immunosuppressive gene in vitro and then returning them to the subject has been widely applied for inducing immune tolerance in vivo (p. 3, 2nd para.). Furthermore, although the preferred embodiments of Yang are directed to inducing immune tolerance in a subject’s brain tissue, and they are silent to inducing immune tolerance in a subject’s liver tissue.
With respect to instant claims, Forbes teaches and claims M2-like macrophage-based cell therapies for inducing immune tolerance in a subject’s liver tissue (Title, Abstract, Brief Summary of the Disclosure, claims 1-10 of Forbes).
Specifically, in regard to claims 6-8, Forbes teaches the subject has acute liver injury and failure (ALF) (Background, col 11, 1st para., col 22, last para., to col 23, 3rd para., see claim 2 of Forbes). In regard to claim 10-12, Forbes teaches the M2-like macrophages reduce inflammation, reduce hepatic fibrosis, and stimulate hepatic regeneration (cols 9-10, Detailed Description). Note as stated above, the scope of the reduction is unclear as to what tissues and conditions are being compared.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice cell therapy methods comprising transfecting macrophages with the immunosuppressive gene such as RNF41 in vitro and then returning them to the subject for inducing immune tolerance in vivo as suggested by Yang, and do so in a subject with liver tissue injury as taught by Forbes with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Forbes because injured liver tissue responds to M2-like macrophage cell therapy with reduced inflammation, reduced fibrosis, and regeneration.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (CN 1119450576A, filed 7/27/2020, published 10/30/2020), in view of Forbes et al., (US 11,285,174, filed 9/18/2017, patented 3/29/2022), as applied to claims 1, 6-8, in further view of Kauffman et al. (Hepat Surg Nutr, 2014, 3:238-246)
As discussed previously, Yang in view of Forbes suggest a method of inducing M2-like macrophage morphology in a macrophage comprising contacting a macrophage with a composition comprising a polynucleotide encode RNF41, and then administering the M2-like macrophage to a subject with liver tissue injury and ALF.
However, Yang and Forbes are silent to the subject having liver tissue injury and failure after a partial hepatecomy.
In regard to claim 9, Kauffman reviews liver injury and failure after major hepatic resection leads to mortality rates as high as 30%, and post-hepatectomy liver failure remains one of the most serious complications of major liver resection (Introduction).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice M2-like cell therapy methods to treat liver injury and failure as suggested by Yang in view of Forbes, and do so in a subject who has undergone a partial hepatectomy as taught by Kauffman with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Kauffman because livery injury and failure is a major source of morbidity and mortality after liver resection (Introduction).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631