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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicants elected a therapeutic of treatment using SEQ ID 2 to treat a patient population of ovarian cancer suffers without traverse in the reply filed on 14 Nov, 2025.
Claims Status
Claims 1-4, 11, 13, 15, 17-19, 22-25, 28, 29, 31-34, 36, and 38 are pending.
Claims 1, 2, and 4 have been amended.
Claim 38 is new.
Claims 3, 11, 13, 15, 17-19, 22-25, 28, 29, 31-34, and 36 have been withdrawn due to an election/restriction requirement.
Maintained/Modified Rejections
Drawings
The drawings are objected to because fig 2b, 4b, 5d, 7a, 7d, 7e, 8b, 8c, 9c, 10H, 10i, 17d, and 17g require color. Some of these figures use a color scale to show data, others use different colors to show different groups, which are too poorly resolved to follow when converted into greyscale. If applicants are unable to correct this issue without color, they can petition for color drawings. 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.
response to applicant’s arguments
Applicants have stated that they have petitioned for color drawings.
Applicant's arguments filed 23 March, 2026 have been fully considered but they are not persuasive.
Applicants have petitioned for color drawings, but the petition has not been granted. Once it has been, the objection will be withdrawn.
Withdrawn Rejections
The rejection of claims 1, 2, 4, and 5 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of written description is hereby withdrawn due to amendment.
The rejection of claim 4 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is hereby withdrawn due to amendment.
The rejection of claim(s) 1 and 4 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (J. Exp. Clin. Canc. Res. (2019) 38(167)) is hereby withdrawn due to amendment.
The provisional rejection of claims 1, 2, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of copending Application No. 17/275,061 is hereby withdrawn due to amendment.
The provisional rejection of claims 1, 4, and 5 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of copending Application No. 18/061,369 is hereby withdrawn due to amendment.
The rejection of claims 1, 2, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 5 of U.S. Patent No. 12,246,004 is hereby withdrawn due to amendment.
The provisional rejection of claims 1, 2, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 9 of copending Application No. 19/002,178 is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(a)
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, 2, 4, and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating susceptible cancers, does not reasonably provide enablement for treatment of all cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The MPEP states “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue.’ These factors include, but are not limited to: 1) the breadth of the claims; 2) the nature of the invention; 3) the state of the prior art; 4) the level of one of ordinary skill; 5) the level of predictability in the art; 6) the amount of direction provided by the inventor; 7) the existence of working examples; and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure” (MPEP 2164.01(a).
1 and 2) the breadth of the claims and the nature of the invention: Applicants are claiming a method of treating cancer based on inhibiting the XPR1:KIDINS220 interaction. A dependent claim (claim 2) limits the patient population to sufferers of ovarian, uterine, breast, bile duct, liver, and lung cancers.
3) the state of the prior art: Chen et al teaches that XPR1 overexpression promotes proliferation, invasion, and resistance to chemotherapy in tongue squamous cell carcinoma, and activates NF-kB signaling in that cancer (2nd page, 2nd column, 1st paragraph).
Cai et al (Int. J. Mol. Med. (2017) 40 p965-971) teaches that the regulatory role of KINDINS220 in cancer is tumor specific (p968, 2nd column, 3d paragraph). For example, in a pediatric high grade glioma, the protein was a tumor suppressor (p969, 2nd column, 3d paragraph) and knockdown of the protein had no effect on neuroblastoma cells (p698, 2nd column, 3d paragraph, continues to p699, 1st column, 1st paragraph). However, a different experiment showed a decrease growth rate in neuroblastoma cells after KINDINS220 knockdown (p699, 1st column, 1st paragraph). In other words, while it is clear that the protein is important in some cancers, so much so that Cai et al suggests investigation into targeting it (p969, 2nd column, 4th paragraph), it clearly is not having much effect on many cancers.
Cmarik et al (Viruses (2011) 3 p2442-2461) discusses screening cancer cell lines for infectious retroviruses (p2443, 1st paragraph). Immunoblotting and PCR found a viral Env protein detected by an antibody to XMVR (p2445, 2nd paragraph). This virus was able to infect other cells (p2447, 1st paragraph). Nor is this the only cell line that produces a similar retrovirus; about 2.2% of a large number of cell lines were positive for XMLV gag sequence by PCR (p2445, 1st paragraph).
Ayen et al (Int. J. Mol. Sci. (2018) 19 1930) discusses gene therapy for ovarian cancer (title). This is not a single cancer, but rather a group of different diseases with differences in epidemiologic and risk factors, molecular events, response to chemotherapy, and prognosis (1st page, 1st paragraph).
4) the level of one of ordinary skill: The level of one of ordinary skill in the art is high.
5) the level of predictability in the art: Russell (Fred Hutch news release (2016)) mentions that President Nixon declared war on cancer, but it is still the second leading cause of death in the US (2nd page, 1st paragraph). Cai et al suggested that the effects of KINDINS220 is very tumor specific. This suggests a low level of predictability.
6 and 7) the amount of direction provided by the inventor and the existence of working examples: Applicants state that XPR1 inactivation had no effect on most cell lines, while 15 out of 63 ovarian or uterine cancer lines were susceptible (paragraph 338). Multicomponent analysis suggested that upregulation of SCL34A2 is what made the difference, but how significant is not clear – it states r= 0.391, r squared= 0.33 (paragraph 339) or total control, i.e. high SCL34A2 expression led to sensitivity to XPR1 inactivation and low expression meant immunity (paragraph 340), that overexpressing SCL34A2 is both necessary and sufficient to confer XPR1 dependency (paragraph 341) i.e. r= r squared=1.
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: It is abundantly clear that applicant’s invention will not work for all cancers. Cmarik et al teaches that about 2.2% of all cancer cell lines produce a virus that has an Env protein that binds to XPR1, but they evidently survive just fine. Applicants state that the invention works for ovarian and uterine cancer when SCL34A2 is upregulated (degree of upregulation not specified), and is essentially ineffective in other cells. However the strength of the correlation appears to be highly variable, depending on what applicants are discussing. But, the prior art lists additional cancers that are treatable by hitting these proteins. Chen et al states that XPR1 plays a critical role in tongue squamous cell carcinoma, which applicants suggests will not be susceptible to their invention, and suggests targeting that protein. Cai et al teach that KIDINS220 inhibition produces very tumor specific results, but discusses potentially targeting the protein in a number of cancers. Making things more complex, Ayen et al states that even a single type of cancer, ovarian cancer, is not really a single disease, but a family of disorders, with different responses to chemotherapy. In other words, we can’t generalize to types of cancers, because each type is actually multiple diseases that react differently to the same treatments. Based on the evidence, XPR1 and KIDINS220 is important in some cancers, and not important in others, but the inconsistencies in applicant’s specification and between their disclosure and the prior art makes it difficult to determine which cancers can be effectively treated by applicant’s claimed method without undue experimentation.
response to applicant’s arguments
Applicants argue that they have narrowed the claims to specific cancers, which the invention is enabled for.
Applicant's arguments filed 23 March, 2026 have been fully considered but they are not persuasive.
The rejection clearly shows that the susceptibility of tumors to this therapy varies from tumor to tumor, and not type of cancer to type of cancer. Note that Cmarik et al (cited in rejection) discusses a lung adenocarcinoma that hosts a virus that expresses the therapeutic used in applicant’s claimed method (title), which will presumably be immune to the therapy.
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.
Claim(s) 1, 2, 4, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Federico (WO 2006106435) in view of McGuire et al (Brit. J. Canc. (2003) 89 (Suppl 3) p53-58).
Federico discusses using a fusion protein with the HIV-1 Nef protein in the field of cancer (p1, 1st paragraph), and has antitumor properties (4th page, 3d paragraph). This can be used as a viral particle comprising an expression vector of the protein (5th page, 1st paragraph), such as MLV (p5, 2nd paragraph). Currently, MLV based vectors are the most frequently used system for gene delivery (p20, 2nd paragraph). Viruses with the ecotropic envelop can only infect mouse cells, but those with the xenotropic envelope can infect other species (p20, 3d paragraph), making it a reasonable choice for a gene delivery system for humans. In vivo use of these viral vectors is explicitly discussed (p32, 6th paragraph, continues to p33, 1st paragraph).
The difference between this reference and the examined claims is that this reference does not specify the cancer type.
McGuire et al discuss the standard of care for ovarian cancer (title). The first choice is surgery, which includes debulking for advanced cancers to improve the efficacy of chemotherapy (p53, 2nd column, 1st paragraph). Chemotherapy is taxanes and platinum compounds (p53, 2nd column, 2nd paragraph). However, most patients with advanced ovarian cancer die of the disease (p57, 2nd column, 4th paragraph). Further improvements in survival may result from incorporation of other reagents (p57, 2nd column, 4th paragraph).
Therefore, it would be obvious to use the therapy of Federico for the patients of McGuire et al, as Federico discusses treatment of a genus (cancer patients) that includes the patients of McGuire et al (ovarian cancer patients). As McGuire et al explicitly suggests incorporation of additional reagents, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Federico discusses using XMLV in the context of cancer, which comprises applicant’s elected species (XMLV envelope protein), which will necessarily bind to XPR1 and inhibit the phosphate export. This renders obvious claims 1, 4, and 38.
McGuire et al renders obvious ovarian cancer for the treatment of Frederico, rendering obvious claim 2.
response to applicant’s arguments
Applicants argue that the rejection misses the limitation of inhibiting XPR1:KINDINS220 mediated phosphate export.
Applicant's arguments filed 23 March, 2026 have been fully considered but they are not persuasive.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer (MPEP 2112(I), quoting Atlas Powder Co v IRECO Inc). But that is exactly what applicants are arguing. Federico teaches using a composition comprising the formulation of applicant’s claimed method. As noted in the rejection, this will necessarily have the same effect.
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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