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 treating a cancer patient with a KRas mutation with SEQ ID 1 and gemcitabine in injectable form without traverse in the reply filed on 9 April, 2026.
Claims Status
Claims 1, 2, 4-8, 10, 14, and 20-22 are pending.
Claims 1 and 8 have been amended.
Claims 2, 4, 8, 10, 14, and 22 have been withdrawn due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claim(s) 1, 5-7, and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Nishi et al (US 20150307574) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
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.
first rejection
Claim(s) 1, 5-7, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Wiersma et al (Autophagy (2015) 11(8) p1373-1388, cited by applicants) in view of Nishi et al (US 20150307574, cited by applicants).
Wiersma et al discuss the effect of galactin-9 on KRas mutant colon cancer (title). The protein is rapidly internalized, killing the cells by halting autophagy (p1374, 1st column, 4th paragraph). This is probably because KRas mutation impairs normal lysosomal composition and function (p1384, 1st column, 2nd paragraph). The invention was also shown to work in an in vivo mouse model, inhibiting tumor growth and increasing overall survivial (p1378, 1st column, 2nd paragraph). Treatment was performed 3x/week, by IP injection (p1387, 1st column, 2nd paragraph).
The difference between this reference and the examined claims is that this reference does not discuss a variant of galactin-9 used in the examined claims.
Nishi et al describe galactin-9 variants for treatment of malignant tumors (paragraph 75). These variants are more stable to proteases, and give a higher yield when recombinantly produced (paragraph 3). Specific examples of galactin-9 variants that can be used in the invention include SEQ ID 42 (paragraph 42 and table 3), identical with SEQ ID 1 of the examined claims. The material can be formulated with carriers (paragraph 84) for injection (paragraph 83), IV, IM, subQ, ir IP (paragraph 79).
Therefore, it would be obvious to use the galactin-9 variants of Nishi et al, as they are more stable to proteases and easier to recombinantly produce. As both Nishi et al and Wiersma et al use their compounds to treat cancers, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Wiersma et al discuss treatment of KRas positive cancers with galactin-9. Nishi et al render obvious using SEQ ID 1 of the examined application. Thus, the combination of references renders obvious claims 1, 3, 20, and 21.
Wiersma et al discusses IP injection, which requires a carrier (peptides are solids and cannot be injected), rendering obvious claims 5-7.
response to applicant’s arguments
Applicant argues that, because the various compounds of Nishi et al have different levels of efficacy, there is no reasonable expectation of success, that KRAS mutations are especially difficult to treat, and claim unexpected results of improved efficacy compared to native galactin-9.
Applicant's arguments filed 7 Aug, 2026 have been fully considered but they are not persuasive.
Applicant argues that there is no reasonable expectation of success, because other galactin-9 variants were shown by the prior art to be less effective. Even if this argument was persuasive, it would not overcome the rejection. While some galatin-9 variants are less impressive, they are still effective at treating cancer, which is the measure of success.
Applicant argues that KRAS mutations are especially difficult to treat. This has not been established; the reference that applicant has cited discusses direct inhibition of mutated KRAS, not treatment of cancers with KRAS mutations. Furthermore, even if it is accepted, Wiersma et al explicitly states that galatin-9 can treat a cancer with mutated KRAS.
Finally, applicant argues alleged unexpected results of improved activity vs. native galactin-9. First, the data that applicant presents is an experiment commonly used to emphasize small differences and shows only a small difference; it is not clear if this difference is of practical significance (MPEP 716.02(B)(I)), or if it is large compared to the variability across different cell lines. Nor is it clear if the data is of statistical significance (MPEP 716.02(b)(I)). Nor is it clear why, if this is of practical and statistical significance, it would be unexpected. The data that applicant presents from Nishi et al in their arguments with respect to expectation of success clearly shows that the congener of galactin-9 that applicant has elected is superior to native galactin-9 in a different test.
second rejection
Claim(s) 1, 5-7, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Wiersma et al (Autophagy (2015) 11(8) p1373-1388, cited by applicants) in view of Nishi et al (US 20150307574, cited by applicants) and Geller et al (Science (2017) 357 p1156-1160).
Wiersma et al discuss the effect of galactin-9 on KRas mutant colon cancer (title). The protein is rapidly internalized, killing the cells by halting autophagy (p1374, 1st column, 4th paragraph). This is probably because KRas mutation impairs normal lysosomal composition and function (p1384, 1st column, 2nd paragraph). The invention was also shown to work in an in vivo mouse model, inhibiting tumor growth and increasing overall survivial (p1378, 1st column, 2nd paragraph). Treatment was performed 3x/week, by IP injection (p1387, 1st column, 2nd paragraph).
Nishi et al describe galactin-9 variants for treatment of malignant tumors (paragraph 75). These variants are more stable to proteases, and give a higher yield when recombinantly produced (paragraph 3). Specific examples of galactin-9 variants that can be used in the invention include SEQ ID 42 (paragraph 42 and table 3), identical with SEQ ID 1 of the examined claims. The material can be formulated with carriers (paragraph 84) for injection (paragraph 83), IV, IM, subQ, ir IP (paragraph 79).
As noted above, these references render obvious claims 1, 3, 5-7, and 20.
The difference between these references and applicant’s elected species is that these references do not discuss gemcitabine.
Geller et al discuss how bacteria mediate tumor resistance to gemcitabine (title), using a colon cancer model (abstract). The bacteria metabolize the drug to an inactive metabolite (1st page, 3d column, 3d paragraph). By killing the bacteria with an antibiotic, gemcitabine was more effective in a murine model of colon cancer (fig 3, 3d page, top of page and 3d page, 3d column, 2nd paragraph, continues to 4th page, 1st column, 1st paragraph). This reference shows that gemcitabine is effective in treating colon cancers, the cancer of Wiersma et al.
Therefore, it would be obvious to add gemcitabine to the therapy of Wiersma et al and Nishi et al, to provide additional therapeutic efficacy. As Geller et al shows that this therapeutic is useful for these cancers, an artisan in this field would attempt this therapy with a reasonable expectation of success. Note that this is a combination of compositions each of which is known to be useful for the same purpose, which is not a patentable distinction (MPEP 2144.06).
response to applicant’s arguments
Applicant argues that claim 8 has been amended to include a synergistic combination.
Applicant's arguments filed 7 Aug, 2026 have been fully considered but they are not persuasive.
Applicant has amended claim 8 so that it no longer covers applicant’s elected patient population, but rather, a subgenus of that population. As applicant was required to elect a single, discrete, and disclosed patient population, and did not elect the patient population of claim 8, as amended, this claim has been withdrawn. Thus, this argument has not been further examined.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
first rejection
Claims 1, 5-7, 20, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 18 of copending Application No. 19/295,090 (US 20260083671) in view of Wiersma et al (Autophagy (2015) 11(8) p1373-1388, cited by applicants) and Geller et al (Science (2017) 357 p1156-1160).
Competing claim 1 describes a formulation of galactin-9 and a buffer (i.e. carrier), while competing claim 2 specifies that the galatcin-9 is SEQ ID 1, identical with SEQ ID 1 of the examined claims. Competing claim 18 specifies an intended use of cancer treatment, anticipating claims 1, 5, and 7.
The difference between the competing claims and the remaining examined claims is that the competing claims do not mention KRas, or a second therapeutic.
Wiersma et al discuss the effect of galactin-9 on KRas mutant colon cancer (title). The protein is rapidly internalized, killing the cells by halting autophagy (p1374, 1st column, 4th paragraph). This is probably because KRas mutation impairs normal lysosomal composition and function (p1384, 1st column, 2nd paragraph). The invention was also shown to work in an in vivo mouse model, inhibiting tumor growth and increasing overall survivial (p1378, 1st column, 2nd paragraph). Treatment was performed 3x/week, by IP injection (p1387, 1st column, 2nd paragraph).
Geller et al discuss how bacteria mediate tumor resistance to gemcitabine (title), using a colon cancer model (abstract). The bacteria metabolize the drug to an inactive metabolite (1st page, 3d column, 3d paragraph). By killing the bacteria with an antibiotic, gemcitabine was more effective in a murine model of colon cancer (fig 3, 3d page, top of page and 3d page, 3d column, 2nd paragraph, continues to 4th page, 1st column, 1st paragraph). This reference shows that gemcitabine is effective in treating colon cancers, the cancer of Wiersma et al.
Therefore, it would be obvious to use the therapeutic of the competing claim to treat the colon cancer of Wiersma et al, as a substitution of one known element (the cancer of the competing claims) for another (the KRas mutated colon cancer of Wiersma et al) yielding expected results (treatment of cancer). As both the competing claims and Wiersma et al discuss treating cancer with galactin-9, an artisan in this filed would make this substitution with a reasonable expectation of success.
Furthermore, it would be obvious to add gemcitabine to the therapy of Wiersma et al, to provide additional therapeutic efficacy. As Geller et al shows that this therapeutic is useful for these cancers, an artisan in this field would attempt this therapy with a reasonable expectation of success. Note that this is a combination of compositions each of which is known to be useful for the same purpose, which is not a patentable distinction (MPEP 2144.06).
response to applicant’s arguments
Applicant argues that, as the examined claims are the earlier filed application, this rejection should be withdrawn.
Applicant's arguments filed 7 Aug, 2026 have been fully considered but they are not persuasive.
To withdraw an obvious type double patenting rejection based on the filing date of the different applications requires, among other things, that the double patenting rejection be the only rejection outstanding. This is not the current fact pattern, as there are two valid rejections under 35 USC 103, above.
second rejection
Claims 1, 5-7, 20, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, and 7 of copending Application No. 19/332,507 (US 20260015394) in view of Shady et al (Oncotarget (2017) 8(39) p66117-66127) and Geller et al (Science (2017) 357 p1156-1160).
Competing claim 1 describes a method of treatment of bone disease with a polypeptide of SEQ ID 1, identical with SEQ ID 1 of the examined claim, while competing claim 3 specifies a Markush group including metastatic bone disease (interpreted as including bone metastases). Competing claim 6 specifies a pharmaceutically acceptable carrier, and competing claim 7 describes a number of administration routes, including oral, IM, IV, IP, and subQ. This anticipates examined claims 1, 5-7, and 20.
The difference between the competing claims and the remaining examined claims is that the competing claims do not discuss KRas status, or a second therapeutic.
Shady et al discuss Kras status in the context of colorectal cancer (title). Colorectal metastases patients have a shorter survival time with Kras mutations (abstract). About 16% of the Kras positive patients also had bone metastases (p66122, 1st column, 1st paragraph). This reference discusses a patient cohort that reads on the competing claims comprising a KRas positive bone metastasis.
Geller et al discuss how bacteria mediate tumor resistance to gemcitabine (title), using a colon cancer model (abstract). The bacteria metabolize the drug to an inactive metabolite (1st page, 3d column, 3d paragraph). By killing the bacteria with an antibiotic, gemcitabine was more effective in a murine model of colon cancer (fig 3, 3d page, top of page and 3d page, 3d column, 2nd paragraph, continues to 4th page, 1st column, 1st paragraph). This reference shows that gemcitabine is effective in treating colon cancers, the cancer of Shady et al.
Therefore, it would be obvious to use the method of the competing claims, as a substitution of one element (the cancers of Shady et al) for another (the cancers of the competing claims) yielding expected results (treatment of cancers). As the cancers of Shady et al are a subgenus of the cancers of the competing claims, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to add gemcitabine to the therapy of the Shandy et al, to provide additional therapeutic efficacy. As Geller et al shows that this therapeutic is useful for these cancers, an artisan in this field would attempt this therapy with a reasonable expectation of success. Note that this is a combination of compositions each of which is known to be useful for the same purpose, which is not a patentable distinction (MPEP 2144.06).
response to applicant’s arguments
Applicant points to the arguments with respect to the rejections under 35 USC 103, above, which were answered there.
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.
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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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