DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-10 are pending.
Priority
This application is filed 07/10/2024, and claims the benefit of domestic priority as below:
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Information Disclosure Statements
One IDS(s) received on 7/10/2024 has been considered unless marked with a strikethrough.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
The lines, numbers and lettering are not clean, well-defined, sufficiently dense and dark, and uniformly thick and well defined in Figure(s) 1, 2 and 4-8. See 37 CFR 1.84(l) and (q). The texts in the graphs, in particular, have significant small and blurry, making them difficult to read/interpret.
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard
consistent with the specification (See MPEP 2111).
Claims 1-10 are drafted as “use” claims, which raise separate issues under 35 USC 101 and 112(b). Nevertheless, for purposes of examination, the claims are interpreted as encompassing methods of using quinoline-4-carboxylic acid (QCA) to achieve the respective biological of therapeutic effects recited therein.
Claim Rejections - 35 USC § 112, Enablement
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 1-6, 9 and 10 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 utilizing quinoline-4-carboxylic acid (QCA) activity in the selection of aging models including mice and mouse liver resection models for studying survival and liver regeneration following liver resection, does not reasonably provide enablement for broadly encompassed "anti-aging products" and "liver protection products" without limitation to the. 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 additional limitations of the dependent claims 2-5, 9 and 10 do not overcome the lack of enablement of the broader subject matter of invention encompassed by claims 1 and 6.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of the invention:
The invention is drawn to biological and therapeutic uses of QCA. Claim 1 broadly concerns the use of QCA in the preparation of an anti-aging product, while claim 6 broadly concerns the use of QCA in the preparation of a liver protective product. Therefore, in view of the claim interpretation, the claimed utility depends on QCA producing the recited biological effect in the relevant biological context, rather than the preparation of administration of QCA.
Breadth of the claims:
The claims are broadly recited an “anti-aging product” without limitation to a particular aging mechanism, tissue, physiological endpoint, species, or treatment condition.
López-Otín et al. (The hallmarks of aging, Cell., 153(6), 1194-217, pub’d 11/21/2013) describes aging as a multifactorial process involving distinct but interconnected mechanism, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication (abstract and introduction). The specification shows QCA activity in selected aging related contexts including mesenchymal stem cell aging and selected phenotypes in fruit flies and aged mice. However, these examples do not represent the full range of aging mechanisms and biological contexts encompassed by claim 1.
Claim 6 similarly recited a “product for protecting liver” broadly without limitations including a particular cause, type, or mechanism of liver injury. Russmann et al. (Current concepts of mechanisms in drug-induced hepatotoxicity, Curr. Med. Chem., 16(23), 3041-53, pub’d 8/16/2009) describes liver injury as arising through materially different mechanisms, including direct cellular stress, mitochondrial impairment, and immune reactions (abstract and introduction). The specification demonstrates QCA activity in a partial hepatectomy model involving liver injury and regeneration. However, claim 6 encompasses liver protection beyond that particular injury setting.
Thus, the functional breadth of claim 1 and 6 exceeds the biological contexts represented by the disclosed examples.
Level of ordinary skill in the art:
The level of ordinary skill in the relevant biomedical and pharmaceutical arts is relatively high and would include knowledge of pharmacology, cell biology, aging biology, liver physiology, and appropriate experimental models.
However, a high level of artisan does not make an otherwise unpredictable biological response predictable. In physiological and pharmacological arts, the scope of the required enablement varies inversely with the degree of predictability involved. See MPEP 2164.03; in re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970)
Accordingly, even a skilled artisan could not rely solely on the disclosed examples to predict QCA activity throughout the substantially broader scope of claims 1 and 6.
State of the prior art and predictability in the art:
As discussed above, the relevant biological and therapeutic arts are unpredictable.
With respect to claim 1, López-Otín shows that aging involves multiple biologically distinct mechanisms. The specification does not establish that QCA affects each of the multiple biologically distinct mechanisms or that activity observed in mesenchymal stem cells, fruit fries, and aged mice reliably predicts anti-aging activity in other tissues, mechanisms, or physiological.
With respect to claim 6, Russmann shows that liver injury may arise through materially different mechanisms. The specification does not establish that QCA activity following partial hepatectomy predicts a protective effect against mechanistically distinct forms of liver injury.
Therefore, there is no disclosed or established predictive relationship that would allow a skilled artisan to extrapolate the reported QCA effects to the full scope of claims 1 and 6 with reasonable expectation of success. In addition, pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction provided and working examples:
For claim 1, the specification provides QCA activity in mesenchymal stem cells and selected aging related phenotypes in fruit fries and mice, and these examples support the specific test conditions. In view of López-Otín, the specification does not provide predictive principles, biomarkers, or selection criteria for determining which of the substantially different aging conditions encompassed by claim 1 would respond to QCA.
For claim 6, the specification reports beneficial QCA effects in a partial hepatectomy model, including effects associated with liver injury, survival, and regeneration. However, in view of Russmann, it does not provide representative working examples involving cases where the causes or mechanisms of liver damage are substantially different, nor does it offer predictive correlations demonstrating that the disclosed results are applicable to such differing situations. See MPEP 2164.02 (“Compliance with the enablement requirement of 35 USC 112, first paragraph, does not turn on whether an example is disclosed ... Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”).
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. See MPEP 2164.01 and 2164.06.
For claim 1, in view of López-Otín, a skilled artisan would need to determine whether QCA produces an anti-aging effect across materially different aging mechanisms, tissues, physiological endpoints, and biological contexts.
For claim 6, in view of Russmann, a skilled artisan would need to test QCA in mechanistically distinct liver injury models, determine appropriate treatment conditions and injury specific endpoints, and establish experimentally whether QCA actually provides a protective effect in each untreated context.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Claim Rejections - 35 USC § 112
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.
Claims 1-10 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.
Claims 1-10 are recited as "use" claims to use of QCA in the preparation of specified products. However, the claims do not recite process steps defining how the recited use is carried out. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05(q), and Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). Accordingly, claims 1-10 are indefinite because they recite a use of QCA for preparation of specified products without setting forth any active steps defining how the claimed use is practiced, such that the metes and bounds of the claimed process are unclear.
Regarding claim 5, the phrase "enhancing exercise capacity and muscle strength" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear because the claim does not provide a boundary for determining when the recited enhancement has been achieved. In particular, the claim does not specify the baseline against which enhancement is determined or the degree of improvement required to satisfy the claimed limitation. Although, the specification describes fruit flies’ climbing assay for evaluating exercise capacity and a grip strength assay for evaluating muscle strength in aged mice (Fig 6B and 7B), claim 5 is not limited to those assays or experimental conditions. Further, the specification does not establish an objective threshold or magnitude of change that constitutes “enhancing” exercise capacity or muscle strength across the scope of the claim.
Regarding claims 8-10, the phrase "improving the survival rate after hepatectomy" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear because the claims do not provide an objective boundary for determining when the recited improvement has been achieved. Although, the specification reports a survival curve for aged mice subjected to 2/3 partial hepatectomy and treated with QCA (paragraph [0054]) , the claims are not limited to that animal model, dosing regimen, control group, or experimental protocol. The claims also not specify the magnitude of improvement required to satisfy the limitation. Thus, the particular experiment data shown in Fig. 8C do not establish a claim wide objective standard for determining when survival is considered “improved”.
Claims 9 and 10 recite the limitation "wherein the product for protecting liver, the product for promoting liver regeneration, and the product for improving the survival rate after hepatectomy" in the middle of claims. There is insufficient antecedent basis for this limitation in the claim. The claims recite all three categories of claims 6-8 regardless of which one of claims is incorporated. For example, when claim 9 is considered as depending from claims 6, whether the additional limitations directed to the products of claims 7 and 8 are also intended to be required limitations of that embodiment.
Regarding claim 10, the phrase "reducing liver injury" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear because the claim does not provide an objective boundary for determining when the recited reduction has been achieved. In particular, the claim does not specify the baseline against which the reduction is determined, the particular indicator or indicators used to assess liver injury, or the magnitude of reduction required to satisfy the claimed limitation. The specification reports that QCA reduced liver injury enzymatic indices, including ALT, AST and LDH, in a mouse partial hepatectomy model. However, claim 10 is not limited to those particular biomarkers, experimental conditions, treatment conditions, or comparison groups. Thus, the scope of the claimed limitation cannot be determined with reasonable certainty.
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 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because claims 1-10 recite "use" claims to the use of QCA in the preparation of specified products, rather than as claims to a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 "). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967). See MPEP 2173.05(q).
Art of Record but not Applied
Zeng et al. (8-Hydroxyquinoline derivatives induce the proliferation of rat mesenchymal stem cells (rMSCs)., Bioorg. Med. Chem., 14(16), 5446-50, pub’d 05/30/2006) is considered the one of the closest art for claim 1. Zeng teaches that 8-hydroxyquinoline derivatives effects on the proliferation of the rat marrow-derived mesenchymal stem cells (rMSCs). However, Zeng does not teach QCA itself that has an anti-aging effect, reducing nuclear DNA damage, and enhances exercise capacity and muscle strength. Thus, Zeng does not provide sufficient working examples to qualify as 103 prior art.
Marciniak et al. (Kynurenic Acid Protects against Thioacetamide-Induced Liver Injury in Rats., Anal. Cell Pathol. (Amst), 2018, 1270483, pub’d 09/20/2018) is considered the one of the closest art for claim 6. Marciniak teaches that the hepatoprotective role of Kynurenic acid (KYNA) in an animal model of liver failure was documented and the use of KYNA in the treatment of Acute liver failure (ALF). Kynurenic acid has a hydroxyl group at position 4 and a carboxylic acid group at position 2, whereas quinoline-4-carboxylic acid has its sole carboxylic acid group at position 4 with no hydroxyl substituent. Marciniak does not teach that the hepatoprotective function proposed by Marciniak can be predictably maintained even if the position of the carboxylic acid group is altered and the hydroxyl substituent is removed. Thus, Kynurenic does not provide sufficient working examples to qualify as 103 prior art.
Conclusion
Claims 1-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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