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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 31, 2025 has been entered.
Claim Status
Claim listing filed on December 31, 2025 is pending. Claims 3-9, 11-16, 18, 20-57, 59-61, 63-64, 66, 69-80, 82-86, and 88-107 are canceled. Claims 1-2 are amended. Claims 58, 62, 65, 67-68, 81, and 87 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species in the election response filed March 7, 2025. Claims 1-2, 10, 17, and 19 are examined upon their merits.
Withdrawn Claim Rejections
Applicant’s cancelation of Claim 12 has rendered all previous rejections directed to this claim moot.
The rejection of Claim 2 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments. There is now proper antecedent basis for “the gel-based inulin formulation.”
The rejection of Claims 1-2, 10, 12, 17, and 19 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is withdrawn in view of Applicant’s amendments. Amended Claim 1 is no longer directed to administering a vaccine that prevents cancer.
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claims 1-2 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the cancer immunotherapy or vaccine” in line 16 (emphasis added), and Claim 2 recites “the vaccine” in line 3. There is insufficient antecedent basis for “the vaccine” in the claims, because “vaccine” was deleted from Claim 1 line 4.
Note, “a CTLA-4 or PDL1 blocking agent” in Claim 1 is not indefinite functional language, because CTLA-4 and PDL1 blocking agents were well-understood and commercially available prior to the effective filing date as evidenced by Buchbinder et al. Am J Clin Oncol 2016 (Table 1).
Note, “such as lymphomas and leukemias” in Claim 1 is not indefinite exemplary language (MPEP § 2173.05(d)) because the broadest reasonable interpretation of “other tumors of tissue organs and hematological tumors” encompasses any type of cancer (solid tumors and/or blood cancers). Therefore, “such as lymphomas and leukemias” names examples that are non-limiting to the scope of cancer types listed in Claim 1.
Claim Rejections - 35 USC § 112 (New)
Claims 1-2, 10, 17, and 19 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 cancers known in the art to respond to immune checkpoint inhibitors, does not reasonably provide enablement for the full scope of treating any cancer type (Claim 1). 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 breadth of the claims and nature of the invention:
The nature of the invention is complex, encompassing the treatment of any cancer type (Claim 1). Claim 1 specifically recites “wherein the cancer is one or more of breast, ovarian, prostate, lung, kidney, gastric, colon, testicular, head and neck, pancreas, brain, melanoma, and other tumors of tissue organs and hematological tumors, such as lymphomas and leukemias, including acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, T cell lymphocytic leukemia, and B cell lymphomas.” As stated under 112(b) claim interpretation above, the broadest reasonable interpretation of “other tumors of tissue organs and hematological tumors” encompasses any type of cancer (solid tumors and/or blood cancers). It is of record in the non-final office action filed 04/10/2025 that “treating” is interpreted as alleviating the symptoms or complications of an established disease, delaying the progression of an established disease, and/or curing or eliminating an established disease. Therefore, the inherent results of administering the combination as recited in Claim 1 (“increased anti-tumor efficacy” and “enhanced inhibition of tumor growth”) are directed to treating cancer.
When analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be "given their broadest reasonable interpretation consistent with the specification." See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
The state of the prior art and level of predictability in the art:
The level of predictability in the art depends, most importantly, on whether the claimed invention can be practiced by one of ordinary skill in the art. MD Anderson Cancer Center 2020 teaches that immune checkpoint inhibitors are a standard treatment for melanoma, small cell lung cancer, non-small cell lung cancer, bladder cancer, kidney cancer, stomach cancer, liver cancer, head and neck cancers, and lymphoma (paragraph 3). However, certain cancers including pancreatic cancer, prostate cancer, and glioblastoma have been especially resistant to checkpoint inhibitors (paragraph 4).
The state of the art shows a continued lack of predictability, even after the effective filing date of the instant invention, in administering immune checkpoint inhibitors to treat certain cancer types such as pancreatic, prostate, and glioblastoma. There is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability in treating cancer types that are resistant to immune checkpoint inhibition.
Level of skill in the art:
The level of skill would be high encompassing oncology, immunology, in vivo treatment assays, etc.
Amount of direction provided by inventor and the existence of working examples:
The specification teaches administering anti-PD-1 immune checkpoint inhibitor in combination with inulin in colon cancer models (Examples I-V) and melanoma models (Example XII). The examples show how enhancing the microbiome enhances the activity of the immune checkpoint inhibitor (Fig. 13A-E) (i.e. the immune checkpoint inhibitor has anti-tumor efficacy as a single agent that is enhanced in combination with inulin). However, there are no working examples that demonstrate that inulin can sensitize cancers to immune checkpoint inhibitors that were previously resistant to immune checkpoint inhibition (i.e. cancer types such as pancreatic, prostate, and brain).
A person having ordinary skill in the art would still have to make a substantial inventive contribution in order to treat any type of cancer by administering inulin in combination with an immune checkpoint inhibitor, since there is no guidance within the disclosure as filed pertaining to this embodiment.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
Given that the nature of the claims is in vivo treatment, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials or in animal models, that are predictive of treatment in a representative number of cancer types that are known to be resistant to immune checkpoint inhibition in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the treatment with a reasonable expectation of success.
The instant specification does not enable the invention to treat any type of cancer (Claim 1). A possible amendment to Claim 1 to overcome the enablement rejection could recite “wherein the cancer is one or more of breast, ovarian, lung, kidney, gastric, colon, testicular, head and neck, melanoma, lymphoma, and leukemia.” This potential amendment removes “prostate, pancreas, brain, and other tumors of tissue organs and hematological tumors” for which the specification is not enabled.
Claim Rejections - 35 USC § 103 (Modified, necessitated by amendment)
Claims 1-2, 10, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Wargo WO 2018/064165 (of record) in view of Loh US 6,149,962 (of record) and Marzorati, et al., J. Funct. Foods 2015 (of record) as evidenced by Wiele et al. J Appl Microbiol. 2006 (of record) and Roberfroid et al. J Nutr. 1998.
Amended Claim 1 recites “wherein the administration of 1) the cancer immunotherapy, and 2) the gel-based inulin formulation, results in prolonged gastrointestinal or colonic retention following oral administration relative to non-gel inulin.” This limitation is interpreted wherein the administration results in prolonged gastrointestinal or colonic retention of the gel-based inulin formulation relative to non-gel inulin because it is the gel-based inulin formulation that is administered orally. This limitation is further interpreted as an inherent pharmacokinetic property of gel-based inulin formulations (MPEP § 2112). The teachings of Wargo in view of Loh and Marzorati make obvious administering a gel-based inulin formulation (of record) but the teachings are silent as to the gastrointestinal or colonic retention of gel-based inulin. MPEP § 2112.III-IV states that a rejection under 35 U.S.C. 103 can be made when the prior art product seems to be identical except that the prior art is silent as to an inherent characteristic, and the Examiner must provide rationale or evidence to show inherency.
Wiele compares the difference in prebiotic potency between fructan compounds of low degree of polymerization (DP 2–20; oligofructose) and higher degree of polymerization (DP 3–60; inulin) (page 453, paragraph 3). Wiele concludes that higher DP causes inulin fermentation to be slower which results in more retention in the distal colon compartments (page 459 paragraphs 2-3). Because of this, inulin has a higher prebiotic potency in the distal region of the colon (page 459 paragraph 3). The teachings of Roberfroid further support Wiele and summarize that inulin with a DP>10 are fermented on average half as quickly as inulin with a DP<10 (abstract). Thus, it is clear from the state of the art prior to filing that gel-based inulin which has a higher DP (~20-47) inherently has a slower fermentation rate and more prolonged colonic retention than non-gel inulin that has a lower DP (~10). Wiele and Roberfroid provide evidence that prolonged colonic retention is an inherent property of the gel-based inulin formulations taught by Loh (of record).
Applicant's arguments filed December 31, 2025 have been fully considered but they are not persuasive. Applicant argues that Wargo in view of Loh and Marzorati fail to teach wherein the gel-based inulin exhibits prolonged gastrointestinal or colonic retention following oral administration relative to non-gel inulin. As outlined above, Wiele and Roberfroid provide evidence that prolonged colonic retention is an inherent property of gel-based inulin because it has a higher DP than non-gel inulin. The rejection is maintained because the art of record makes obvious the gel-based inulin formulation and thus the inherent properties thereof. Note, MPEP § 2112.V states that once the Examiner presents evidence and reasoning to show inherency, the burden shifts to the Applicant to prove that the prior art products do not inherently possess the characteristics of the claimed product.
Double Patenting (New)
Claims 1-2, 10, 17, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10-11, 14, 17, 19, 34, 39-40, and 43 of copending U.S. App. No. 18/293,217.
The instant claims recite a method of administering a CTLA-4 or PDL1 blocking agent and a gel-based inulin formulation having an average degree of polymerization between 20 and 47 to a human subject wherein the inulin is administered orally and wherein the cancer is any type of cancer and inherent results thereof (Claims 1 and 19). Dependent claims recite: wherein administration of the inulin occurs prior to, concurrent with, or after administration of the immune checkpoint inhibitor (Claim 2); wherein the gel-based inulin formulation has an average degree of polymerization of approximately 28 and comprises fructo-oligosaccharide (Claim 10); and wherein the method further comprises administering an additional chemotherapy such as a monoclonal antibody (Claim 17).
The copending claims recite a composition comprising one or more biodegradable agents associated with one or more therapeutic agents (Claim 1). Depending claims recite: wherein the biodegradable agent is gel-based inulin having a degree of polymerization between 20 and 47 and wherein the gel-based inulin comprises fructo-oligosaccharide (Claims 8 and 10); the therapeutic agent is an immune checkpoint inhibitor that blocks CTLA-4 or PDL1, specifically an anti-CTLA-4 monoclonal antibody and/or an anti-PDL1 monoclonal antibody (Claims 11, 14, 17) which reads on instant Claim 17; and a method for treating the symptoms of a condition by orally administering the composition to a human subject (Claims 34 and 39-40) wherein the condition is pancreatic cancer, bile duct cancer, gall bladder cancer, or liver cancer (Claim 43).
Because the copending claims recite the same elements of the instant claims, the method of the instant claims is either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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