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 Amendments
Applicant’s amendments to the claims of July 27, 2026, in response to the Office Action of May 8, 2026, are acknowledged.
Response to Arguments
Rejections not set forth below have been withdrawn and/or rendered moot by the amendments to the claims.
With regard to the Provisional DP Rejection, Applicant notes that the claims “are provisionally rejected….over claim 15 of co-pending application 17/928,788….” The examiner notes that this has been withdrawn in view of the cancelation of claim 15 in the ‘788 application.
With respect to the traversal of the § 103 rejection, Applicant argues that Veech discloses higher concentrations of glucose.
The examiner notes that while this may be true, Veech teaches a dialysis fluid that has not been modified to treat cancer, e.g.
Speyer teaches higher concentrations of drug can be delivered safely through dialysis. Sodium bicarbonate was added safely along with anticancer drugs. Martin and Pilon-Thomas are cited to show that the claimed agents are each known to be anticancer agents. More specifically, Martin teaches treating cancer by producing levels of acetoacetate and (R)-3-hydroxybutyrate (i.e., BHB) wherein the total concentrations in the blood are elevated to 0.1 to 30 mM. Pilon-Thomas teaches neutralizing tumor acidity with bicarbonate impaired the growth of some cancer types and combining bicarbonate therapy with immunotherapies improved antitumor responses in multiple models. DeNicola is cited to address the use of a lower concentration of glucose, glutamine, and amino acids thereby providing a motivation to limit these concentrations. In particular, DeNicola teaches tumor cells need glucose and glutamine which they need for proliferation. See Figure 3. Cancer cells uptake glucose, glutamine, and amino acids to fuel their pools of macromolecule precursors to cellular proliferation. See Figure 1. Many cancer cells types use glutamine as a major source of TCA cycle anapleurosis.
As such, there is a motivation with a reasonable expectation of success in arriving at the claimed product for treating cancers. The claimed agents are motivated for use in a hemodialysis fluid product and incorporating anticancer agents and limiting those agents that are beneficial for the growth of numerous cancers is well-motivated. Each claimed agent is a known result-effective variable that is taught to be used in a claimed or similar concentration and could be optimized through nothing more than routine experimentation.
With regard to new claim 10, Veech teaches a composition to have a pH in the range of 5-9. This includes the claimed range. See prior art claims.
With regard to new claims 12 and 13, the claimed product is defined in claim 1 from which claims 12 and 13 depend. There is no subject population nor a method step in a product claimed. There is already a motivation of record to limit the glucose and glutamine as well as amino acids when the hemodialysis fluid is going to be used to treat cancer. Further, Spreyer notes that tumors of the colon, among others, tend to remain localized and therefore seem amenable to administration of drugs into the peritoneal cavity. Thus, while not necessarily structurally limiting in all instances, the prior art provides a motivation to target colon cancers among others with the claimed product.
The claimed structural components are taught by the prior art and there is a motivation to arrive at a product that includes each claimed limitation. There is a further motivation to limit the concentrations of those components claimed to be limited. As such and without a showing of unexpected results, the instant claims remain rejected in view of the prior art set forth below.
With respect to the § 101 rejection, the examiner notes that the claims are directed to a combination of natural products. Claim 1, e.g., requires bicarbonate and acetoacetate. These are two natural products. Applicant has not shown a marked difference in structure, function, or combined properties as compared to those elements as they naturally exist. There is no indication nor showing that the claimed combination at claimed concentrations does anything different than the same combination at the same concentrations of these components as they occur in nature. As such, the examiner is maintaining the § 101 rejection. To overcome this rejection, Applicant can show how the claimed combination will exhibit activity not seen in the individual components or with added feature or functionality that distinguishes over those products in nature. Without such showing or description, the combination is considered to not markedly differ from their natural counterparts. Ratios and amounts are generally insufficient per se to achieve such showing. See https://www.finnegan.com/en/insights/articles/puzzling-out-the-patent-eligibility-of-natural-products.html, Giannelli et al., “Puzzling Out the Patent-Eligibility of Natural Products,” November 9, 2018.
Status of the Claims
Claims 1, 3, 5, 7, and 9-13 are pending and examined.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3, 5, 7, and 9-13 do not fall within at least one of the four categories of patent eligible subject matter because they are naturally occurring compositions of matter.
According to the instant Specification on page 5: Ketone bodies are produced by the liver from fatty acids, including BHB. Further, sodium bicarbonates are produced naturally. Bicarbonate is an ion that is naturally occurring in ground water and surface waters. https://www.hoffmannbros.com/mineral/bicarbonate Goren “Bicarbonate” (date accessed-May 6, 2026); also see Newman et al., “B-Hydroxybutyrate A signaling Metabolite,” Annu Rev Nutr. 2017 August 21; 37:51-76.
Claims 1, 3, 5, 7, and 9-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural products without significantly more.
Claims 1, 3, 5, 7, and 9-13 recites bicarbonate ions and ketones, including BHB, which are present naturally. There is no indication that the composition has any characteristics that are markedly different from the naturally occurring counterpart. The claims do not, therefore, include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP § 2106 sets forth the Subject Matter Eligibility Test to determine if a claim is directed to patent eligible subject matter. Step 1 asks if a claim is directed to a statutory category of invention. Applicant’s claims are directed to a product; thus, the answer to Step 1 is Yes.
The analysis then moves to Step 2A, Prong One, which asks if a claim recites to a product of nature. In this case, instant claims are directed to an amount of naturally occurring products that can be found in nature, and therefore patent ineligible judicial exceptions (natural products) under 35 USC 101.
MPEP § 2106.04(b) states that “When a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation and determine the answer to Step 2A.”
MPEP § 2106.04(c)(I) states that “if the nature-based product limitation is not naturally occurring, for example due to some human intervention, then the markedly different characteristics analysis must be performed to determine whether the claimed product limitation is a product of nature exception…”. To perform the markedly different characteristic analysis, MPEP § 2106.04(c)(II) states “The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties…”.
With respect to the inclusion of amino acids and any cytostatic agent, this is also the inclusion of natural products. For example, curcumin, quercetin, turmeric, etc. Also see Kinghorn et al., “Discovery of Natural Product Anticancer Agents from Biodiverse Organisms,” Curr Opin Drug Disc Devel. 2010 May 27. Many cytostatic agents are known to be natural products. Also see Ling et al., “Cytostatic and Cytotoxic Natural Products against Cancer Cell Models,” Molecules 2019 May 26;24(10):2012.
Therefore, the answer to Step 2A, Prong One, is Yes.
Thus, the analysis must move to Step 2A, Prong Two, which asks if the claim recites additional elements that integrate the judicial exception into a practical application. As discussed in MPEP § 2106.04(d)(2) this evaluation is performed by identifying whether there are additional elements recited in the claim beyond the judicial exception and evaluating these additional elements to determine whether the claim as a whole integrates the exception into a practical application. The additional element is a concentration or amount of a naturally occurring form is not sufficient, per se, to integrate the judicial exception into a practical application. Thus, the answer to Step 2A, Prong Two, is No.
Thus, the analysis must move to Step 2B which asks if claims recite additional elements that amount to significantly more than the judicial exception. MPEP § 2106.05 states that this evaluation is performed by “Evaluating additional elements to determine whether they amount to an inventive concept requires considering them both individually and in combination to ensure that they amount to significantly more than the judicial exception itself.” In this case, the dependent limitations include an amount and/or the addition of amino acids and/or any cytostatic agent. Thus, the answer to Step 2B is No.
As elaborated above, claims 1, 3, 5, 7, and 9-13 do not provide sufficient limitation beyond the judicial exceptions or provide anything that adds significantly more to the judicial exceptions. Consequently, it is not directed to patent eligible subject matter.
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.
Claims 1, 3, 5, 7, and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Veech et al., (U.S. Pat. No. 4,663,166), in view of Speyer et al., “The Use of Peritoneal Dialysis for Delivery of Chemotherapy to Intraperitoneal Malignancies,” Cancer Chemo and Immunotherapy 1980, and in view of Martin et al., (US2008/0249173), and in view of Pilon-Thomas et al., “Neutralization of tumor acidity improves anti-tumor responses to immunotherapies,” Cancer Res. 2016 March 15; 76(6):1381-1390 (cited in ISR), and DeNicola et al., “Cancer’s fuel choice: new flavors for a picky eater,” Mol Cell. 2015 November 19; 60(4): 514-523.
Note on claim interpretation: While the examiner does not object to the phrase “formulated for a hemodialysis therapy method of treating a cancer of a patient” the instant claims are product claims. As such, this phrase will only further limit the claims if it imparts a further structural limitation that is not already recited.
Veech teaches solutions for use in dialysis comprising at least one of three combinations wherein combinations (a) and (c) include bicarbonate and d-betahydroxybutyrate/acetoacetate. See Abstract. Thus, a POSA would immediately envisage the claimed combination in view of the limited combinations taught. The couples described are commonly in the range of 0 to 25 or 0 to 60 mM/liter. Veech claims a solution with about 0.5 to 60 mM bicarbonate as well as up to 55 nM BHB and acetoacetate. See prior art claims 1, 6, 12, and others. There is no requirement that glucose or other amino acid is required in the composition.
With regard to new claim 10, Veech teaches a composition to have a pH in the range of 5-9. This includes the claimed range. See prior art claims.
Veech does not teach incorporating an anticancer agent.
Speyer teaches higher concentrations of drug can be delivered safely through dialysis. Sodium bicarbonate was added safely along with anticancer drugs, including methotrexate and 5-fluorouracil. See p266, last par. “In summary, intraperitoneal administration via peritoneal dialysis is a feasible and interesting route for delivering chemotherapy to patients in whom tumor is confined to the intraabdominal space.” See p269, 2nd par.
Martin and Pilon-Thomas are cited to show that the claimed agents are each known to be anticancer agents.
Similarly, Martin teaches treating cancer by producing levels of acetoacetate and (R)-3-hydroxybutyrate (i.e., BHB) wherein the total concentrations in the blood are elevated to 0.1 to 30 mM. See prior art claim 6.
Similarly, Pilon-Thomas teaches neutralizing tumor acidity with bicarbonate impaired the growth of some cancer types and combining bicarbonate therapy with immunotherapies improved antitumor responses in multiple models. See Abstract.
DeNicola is cited below to further support the notion that glucose, glutamine, and numerous amino acids would be avoided in an anticancer composition. However, they are also not taught as required by any of the cited references.
Furthermore, DeNicola teaches tumor cells need glucose and glutamine which they need for proliferation. See Figure 3. Cancer cells uptake glucose, glutamine, and amino acids to fuel their pools of macromolecule precursors to cellular proliferation. See Figure 1. Many cancer cells types use glutamine as a major source of TCA cycle anapleurosis.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of the prior art. One would be motivated to do so because the claimed ketone bodies and bicarbonate are independently useful as a dialysis fluid and in the treatment of cancers. Further, Veech teaches similar concentrations of ketone bodies and bicarbonate. Moreover, Speyer teaches a formulation that includes a dialysis fluid that includes bicarbonate in addition to a cytotoxic agent. Even further, Martin teaches acetoacetate and BHB concentrations that can be used to treat cancer. Similarly, Pilon-Thomas teaches bicarbonate to neutralize the tumor microenvironment and treat cancers. Finally, while not required by any reference, DeNicola teaches that glucose, glutamine, and numerous amino acids are required for growth and proliferation of cancer cells. As such, a POSA would understand that a combination of BHB, acetoacetic acid, and bicarbonate can be used in a fluid for treating cancer and dialysis and such combination would ideally not include fuel for cancers including many amino acids, glucose, and glutamine. Even further, prior art teaches dosages that overlap the claimed dosages. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
None of the cited references require the amino acids that are excluded and there is no reason to include them in a composition used for the treatment of cancer.
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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