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 .
Priority
This Application is a 371 of PCT/CN2021/143696, filed Dec. 31, 2021, and claims foreign priority to CN202011618811.X, filed Dec. 31, 2020 in the People’s Republic of China.
Formal Matters – Status of the Claims – Response to Restriction/ Election Requirement
Claims 1, 3, 5, and 7-23 are pending.
Applicant’s election without traverse of Group I (claims 1, 12-14 and 21) and ethyl acetate, in the reply filed on Nov. 13, 2025 is acknowledged.
Claims 1, 12-14 and 21 are currently active and subject to examination. Claims 3, 5, 7-11, 15-20 and 22-23 are withdrawn.
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.”
Claim 14 is 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 14 is indefinite because it lists both a product and process(es) in the same claim. Claim 14 is directed towards a pharmaceutical composition and also the process of using the composition. “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011).” (MPEP 2173.05(p)).
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, 12-14 and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Independent claim 1 is directed towards a pharmaceutical composition for “treating or preventing a cancer” comprising an ester compound and DMSO. Claims 12-14 and 21 depend from claim 2, and add limitations regarding ratios and lactic acid, but do not limit the scope of cancers treated.
The enablement requirement refers to the requirement of 35 U.S.C. 112(a) that the specification describe how to make and use the claimed invention (MPEP § 2164). Applying the factors set for in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), one of ordinary skill in the art could not use the claimed invention without undue experimentation:
Nature of the invention: The claimed invention is directed towards pharmaceutical compositions for treating or preventing cancer, comprising DMSO and an ester compound.
Cancer is not a single disease: The compositions are intended to be used in “cancer treatment” generally. However, cancer is not a unitary disease but rather an umbrella term encompassing hundreds to thousands of distinct malignancies arising from different tissues, driven by different genetic mutations and exhibiting different biological behaviors. The specification lists over 80 distinct cancer types (Specification, p. 8), which are fundamentally different diseases at the molecular level.
Cancer therapeutics require target-specific approaches: Modern oncology has moved decisively towards targeted therapeutics and precision medicine precisely because the molecular heterogeneity of cancer renders broad-spectrum approaches ineffective. Successful cancer drugs exploit specific vulnerabilities: HER2 amplification (trastuzumab), BCR-ABL fusion (imatinib), BRAF V600E mutation (vemurafetinib), etc. (e.g. Min & Lee, Exp Mol Med, 2022 Oct 12;54(10):1670–1694). The claimed therapeutic approach premised on simple organic solvents interacting nonspecifically with cell membrane aldehydes runs counter to the established understanding of cancer biology.
The claimed active agents are common solvents: The compositions of claims 1, 12-14 and 21 comprise an ester compound (specifically ethyl acetate) and DMSO. Ethyl acetate is a common industrial solvent used in glues, nail polish removers and decaffeination processes (see, e.g., “Ethyl Acetate”, Celanese, 2013, p. 1-2). It is not commonly known in the art to have therapeutic properties. DMSO is an organosulfur compound approved by the FDA only for bladder instillation for the treatment of interstitial cystitis (see “Dimethyl sulfoxide (intravesical route)”, Mayo Clinic, 2025). While DMSO has been the subject of fringe claims regarding anticancer activity, these claims have not been validated by rigorous clinical evidence and DMSO is not approved or recognized for cancer treatment. DMSO is known to be lethal to mice at doses of 5.0 mL/ kg (White et al., INSTITUTE REPORT NO. 167, Toxicology Series 66, December 1983, p. 1-50). 10% DMSO is also reported to be hepatotoxic and nephrotoxic to rats (Kurdi et al., International Journal For Research In Biology & Pharmacy, Vol. 5, Issue 7, July 2019).
The therapeutic context demands rigorous proof of efficacy: Cancer patients often forgo other treatment options when pursuing a particular therapy. Ineffective treatments carry significant costs: disease progression during wasted time, side effects without benefit, and psychological harm from false hope. The nature of an invention directed towards a cancer therapy demands a higher degree of evidentiary support than might be required in less consequential therapeutic contexts.
History of failed cancer therapies: The pharmaceutical industry has experienced an extraordinarily high failure rate in oncology drug development. This well-documented attrition rate reflects the profound unpredictability inherent in cancer therapeutics and underscores why enablement in this field requires robust data rather than speculation. The nature of this invention- claimed cancer treatment based on common solvents with a single questionable animal study- falls squarely within the category of unpredictable arts where the enablement burden is at its highest (see MPEP 2164.03).
The nature of this invention therefore involves the extraordinary claim that common solvents, when combined become an effective cancer therapy. Such a claim requires correspondingly strong evidentiary support, which the specification does not provide.
Breadth of the claims: The claims encompass treatment of any and all cancers. Claim 1 encompasses any and all ester compounds (thousands of potential compounds). Cancer is not a single disease but rather hundreds to thousands of different diseases with different genetic drivers, tumor microenvironments, and therapeutic vulnerabilities. A composition effective against one type of cancer cannot be presumed to be effective against other cancers.
Predictability in the art: The pharmaceutical and oncology arts are highly unpredictable. It is well established that therapeutic efficacy against one tumor type does not predict efficacy against other tumor types.
Amount of direction provided: The specification provides inadequate direction to enable one of ordinary skill in the art to practice the claimed invention across its full scope.
No guidance on formulation optimization: The Specification lists various ratios of ester compounds to DMSO (1:1 to 1:200) without providing any direction regarding which ratios are effective for what purpose. Examples 1a, 2a and 3a list formulations with different ratios, but provide no data regarding the relative efficacy of these formulations. The single animal study used only a 1:100 ratio. One of ordinary skill in the art is given no guidance on how to select an appropriate ratio for a given therapeutic application or whether the other recited ratios would provide any therapeutic benefit.
No guidance on route of administration: Claim 8 recites oral administration, intravenous drip, intravenous injection and transdermal administration. The single working example used only intragastric administration. The specification provides no data or direction supporting efficacy via other routes. Different administration routes result in different bioavailability, distribution and metabolism profiles. One of ordinary skill in the art cannot extrapolate from intragastric administration in mice to intravenous or transdermal administration in humans without undue experimentation.
No dosing guidance for human subjects: The animal study used doses of 0.54 mg/kg, 2.7 mL/kg and 13.7 mL/kg in mice. The specification provides no direction on how to translate these doses to human subjects, no allometric scaling calculations, and no pharmacokinetic parameters that would allow an ordinary artisan to determine a starting dose for human treatment. The high dose regimen caused 28.6% mortality in mice, yet the specification provides no guidance on how to identify a safe and effective dose in human subjects.
No guidance on treatment duration or regimen: The animal study administered treatment for approximately 19 days. The specification provides no direction on appropriate treatment duration for human cancers, whether continuous or intermittent dosing is appropriate, how long treatment should continue, or what endpoints should guide treatment decisions.
Speculative mechanism without supporting evidence: The specification proposes that the composition targets aldehyde compounds on cell membranes, but provides no direction on how this mechanism operates, what specific aldehydes are involved, how one of ordinary skill in the art could identify target engagement, or how this mechanism relates to the claimed therapeutic effect. Without understanding the mechanism, an ordinary artisan has no principled bases for predicting which cancers might respond to treatment.
No direction linking lactic acid to efficacy: Dependent claim 21 requires that the composition further comprises 4.5 v/v% lactic acid. The specification provides no explanation of what role the lactic acid plays in the composition, why this specific concentration was selected, or how it contributes to therapeutic efficacy. The animal study did not use lactic acid and there is no working example of a composition containing lactic acid and no direction permitting an ordinary artisan to practice this specific embodiment without undue experimentation.
Existence of working examples: The specification provides a single in vivo example using U-87MG human glioblastoma cells in a mouse xenograft model (example 4). This single data point cannot enable treatment across the full breadth of cancers encompassed by the claim.
Quality of the disclosed data: The disclosed experiment raises significant concerns about whether even the single tested cancer type is enabled:
The study lacks a DMSO-only control group. The study employed normal saline as the solvent control. DMSO has been reported in the literature to have biological effects including membrane permeabilization, anti-inflammatory activity, and purported anticancer properties (see, e.g., Deng et al.. J Breast Cancer. 2014 Mar;17(1):25-32). Without a DMSO-only control group, the study cannot establish that the ester compound contributes any therapeutic efficacy beyond what DMSO alone might provide. This is a fundamental design flaw that renders the result uninterpretable with respect to the claimed invention.
The dose-response relationship is inverted: A hallmark of genuine pharmacological activity is a dose-dependent response. Here, the results show the opposite: the low-dose group (37.9% suppression) outperformed the medium dose group (27.1% suppression) (Specification, p. 11) which is inconsistent with a genuine pharmacological effect. This suggests that the observed tumor mass differences are attributable to experimental noise, variability between animals, or confounding factors unrelated to experimental efficacy.
Toxicity confounding high dose results: The high-dose group exhibited overt toxicity. Two of the seven animals died on day 3 with the surviving animals displaying signs consistent with systemic toxicity (reduced body temperature, inactivity, anorexia) (Specification, p. 10). The observed tumor mass reduction may reflect cachexia secondary to toxicity rather than therapeutic efficacy.
State of the prior art: Neither ethyl acetate nor other simple alkyl ester solutions are recognized in the prior art as having anticancer therapeutic properties. The proposed mechanism involving an aldehyde targeting on cell membranes (Specification, p. 4), is not established in the oncology literature and is not experimentally demonstrated in the specification.
DMSO has recognized biological activity but is not an established cancer therapeutic. The prior art contains reports that DMSO has activity against cancer cells. (e.g. Deng et al.. J Breast Cancer. 2014 Mar;17(1):25-32). However, despite decades of investigation, DMSO has not been developed or approved as a cancer therapeutic, and its reported anticancer effects have not translated into a clinical application. The existence of this literature underscores a critical deficiency in the present application: the lack of a DMSO only control group. Because DMSO itself may have anticancer effects, the Specification’s failure to include this control means that one of ordinary skill in the art cannot determine whether the claimed ester compound adds anything beyond DMSO alone.
Single report of ethyl acetate vapor in vitro anticancer activity: There is a report that ethyl acetate vapor can induce cytotoxicity in an in vitro breast cancer cell line (Khan et al., Integrative Medicine Research, Vol. 6, Issue 1, March 2017, p. 47-59). However, this study involved only vapor-phase exposure without direct contact between the compound and the cells, a fundamentally different mode of action from the claimed liquid compositions administered intragastrically. They also report that exposure to vapor of higher concentration ethyl acetate was cytotoxic to normal kidney cells, and that ethyl acetate is known to cause lung, kidney and liver damage.
The prior art reflects the unpredictability of cancer therapeutics. The existence of isolated reports of anticancer activity for DMSO and ethyl acetate, without translation into approved therapeutics, illustrates the well-known unpredictability of cancer drug development. The prior art supports, rather than undermines, the conclusion that an ordinary artisan would require extensive experimentation to determine whether the claimed compositions would have genuine safety and efficacy for the treatment of cancers.
Level of Skill in the Art: A person having ordinary skill in the art would possess an advanced degree (PhD or MD) in oncology, pharmacology, or a related discipline, along with practical experience in cancer drug development. This skilled artisan would readily recognize the methodological flaws in the disclosed experiment and would have no scientific basis upon which to extrapolate from a single flawed glioblastoma experiment to the treatment of all cancers.
Quantity of experimentation: Given the unpredictability of oncology therapeutics and lack of credible data supporting efficacy even in the single tested model, one of ordinary skill in the art would be required to conduct extensive and undue experimentation- essentially a full drug development program- to determine whether the claimed compositions have any utility in treating the broad scope of cancers encompassed by the claims.
Identification of potentially responsive cancer cell types: The claims encompass treatment of any and all cancers without limitation. The specification provides data from only a single cancer cell line (U-87MG glioblastoma). To practice the claimed invention, an ordinary artisan would need to conduct in vitro screening across a representative sample of cancer cell lines- likely dozens to hundreds of lines representing different tissue origins, molecular subtypes, and driver mutations. This screening alone would require substantial time and resources, with no guidance from the specification on the specific types of cancers might respond and why.
Validation that the observed effects are therapeutically relevant: Given the methodological deficiencies in the disclosed experiment, an ordinary artisan would need to repeat the basic efficacy studies with proper controls, including a DMSO only control group, to determine whether ethyl acetate contributes any therapeutic benefit. The artisan would also need to conduct studies at multiple dose levels with adequate sample sizes to establish whether a genuine dose response relationship exists. These studies were not adequately performed by the Applicant.
Mechanistic investigation: The specification proposes a membrane aldehyde targeting mechanism but provides no validation. One of ordinary skill in the art would need to conduct extensive biochemical studies to determine whether the claimed compositions actually interact with membrane aldehydes, identify which aldehydes are involved, establish whether such an interaction occurs at therapeutically achievable concentrations, and if it is casually related to any antitumor effects. Without a mechanistic understanding, rational optimization of the compositions would be impossible.
Formulation optimization: The specification recites ester-to-DMSO ratios ranging from 1:1 to 1:200 but provides efficacy data for only a single ratio (1:100). One of ordinary skill in the art would need to systematically evaluate multiple ratios to determine which, if any, provide a therapeutic benefit for a given cancer type. Given that different cancers may respond differently, these experiments may have to be repeated for each cancer type. For claim 21, which requires 4.55 v/v% lactic acid, an ordinary artisan would need to first establish that lactic acid provides any benefit at all, and what the safety profile is. Lactic acid is safe when used in mouthwashes at a concentration of up to 5% for up to 14 days, but its safety has not been established for oral administration, or when used in combination with other caustic solvents like DMSO. (see, e.g., “Lactic Acid - Uses, Side Effects, and More”, WebMD, retrieved Dec. 2025).
Dose finding-studies: The disclosed animal study demonstrated that the high dose (13.5 mL/kg) caused unacceptable toxicity. The specification provides no guidance on the therapeutic window for the claimed compositions. An ordinary artisan would need to conduct comprehensive dose-ranging and maximum tolerated dose studies in animal models to identify doses that do not have unacceptable toxicity. This would need to be repeated for each route of administration, as bioavailability and toxicity profiles differ based on administration route.
Pharmacokinetic and biodistribution studies: The specification provides no pharmacokinetic data. An ordinary artisan would need to determine the adsorption, distribution, metabolism and excretion parameters for the claimed compositions. This would include determining whether the active components reach tumor tissue at therapeutically relevant concentrations, what the plasma half-life is, how the components are metabolized, and whether metabolites have toxic effects.
Translation to human subjects: Even if animal studies ultimately supported efficacy and safety, the specification provides no guidance on translation to human use. An ordinary artisan would need to develop appropriate human formulations, determine starting doses, and design and conduct clinical trials. Given the fundamental questions about whether the claimed compositions have any genuine therapeutic activity, this clinical development program would be starting from scratch, rather than building on a validated proof of concept.
Aggregate burden constitutes undue experimentation: Considered individually, each category of experimentation described above represents substantial effort. Considered in aggregate, the experimentation required to practice the full scope of the claims would constitute a complete pharmaceutical development program, spanning many years and requiring extensive resources available only to pharmaceutical companies. This is precisely the type of undue experimentation that the enablement requirement was designed to prevent. The patent system was not designed to permit an Applicant to broadly claim common solvent compositions while providing only a single, methodologically flawed data point, leaving the public to conduct extensive experimentation necessary to determine if the claimed invention actually works.
Claims 1, 12-14 and 21 are rejected under 35 U.S.C. § 112(a) for lack of enablement. The specification provides only a single flawed animal study using one composition and one cancer cell line (U-87MG) to support a use for the treatment of all cancers with all compositions comprising DMSO and an ester compound. The study lacks a DMSO-only control, exhibits an inverted dose-response relationship inconsistent with genuine pharmacological activity, and shows toxicity related confounding at the high dose- deficiencies that, combined with the broad scope of the claims, lack of any mechanistic validation, and inherent unpredictability of cancer therapeutics, would require one of ordinary skill in the art to undertake undue experimentation to practice the full scope of the claims.
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.”
Claim(s) 1 and 12-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Korber & Bodmeier (European Journal of Pharmaceutical Sciences, Volume 35, Issue 4, 15 November 2008, Pages 283-292)
Claim 1 is directed towards a pharmaceutical composition for treating or preventing a cancer, comprising an ester compound and dimethylsulfoxide (DMSO).
The purpose or intended use of the composition is not limiting (MPEP 2111.02.II). Therefore, the claim reads on a pharmaceutical composition comprising an ester compound and DMSO.
Korber teaches a pharmaceutical composition (in situ forming drug delivery system) comprising ethyl acetate and DMSO:
The incorporation of the model protein hen egg white lysozyme into liquid in situ forming poly(lactide-co-glycolide) (PLGA) implant or microparticle formulations was investigated. Ternary solvent blends of dimethyl sulfoxide (DMSO), ethyl acetate and water were used to adjust the protein solubility in order to facilitate the incorporation of either dispersed or dissolved protein into the polymer solution. Lysozyme formed large gel particles when dispersed directly in the polymer solution. These formulations had a pronounced initial release. Non-aqueous precipitation of lysozyme from solutions in DMSO with ethyl acetate led to a reversible aggregation without loss in biological activity. Lysozyme could be incorporated in a finely dispersed state through an in situ precipitation by non-solvent or polymer addition. Non-aqueous precipitation could thus be utilized to manufacture biodegradable in situ forming drug delivery systems containing homogeneously distributed and bioactive protein.
Korber, Abstract.
Therefore, claim 1 is anticipated.
Claim 12 is directed towards the pharmaceutical composition of claim 1, wherein the ester compound is a C2-8 lower ester. Claim 13 is directed towards the pharmaceutical composition according to claim 1, wherein the ester compound is ethyl acetate.
As shown above, Korber teaches that the ester compound is ethyl acetate.
Therefore, claims 12-13 are anticipated.
Claim 14 recites: The pharmaceutical composition according to claim 13, wherein a volume ratio of the ethyl acetate to the DMSO is 1:1 to 1:200; and the ethyl acetate and the DMSO are separately diluted with water or mixed and then diluted with water, and then directly administered orally, injected, or sprayed to treat or prevent an animal or human disease.
This claim reads on a pharmaceutical composition comprising ethyl acetate and DMSO at a volume ratio of 1:1 to 1:200 and water. The patentability of a product is not dependent on its method of production (MPEP 2113). Korber teaches a pharmaceutical composition (in situ implants) comprising ethyl acetate and DMSO at a 1:3 ratio, and water:
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Korber, Table 1, p. 289.
Therefore, claim 14 is anticipated.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629