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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 14, 2025 has been entered.
Claims Status and Response to Amendments
The amendments filed October 14, 2025, have been acknowledged and entered. Claims 1, 3, 6-8, 10-11, 13, 15 and 20-25 are pending.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this Office Action has been withdrawn or rendered moot in view of Applicant' s amendments and/or
remarks.
Claim Rejections - 35 USC § 112a
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.
Claim 1, 3, 6-8, 10-11, 13, 15 and 23 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 a method of treating idiopathic pulmonary fibrosis, osteoarthritis, atherosclerosis, skin wounds, and skin aging in a patient, does not reasonably provide enablement for treating kidney disease or liver fibrosis. 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.
“Liver fibrosis” was addressed in the enablement rejection set forth in the previous office action and the arguments are incorporated herein by reference (see pages 5-10 of office action mailed August 28, 2025)
Regarding “kidney disease”, Applicant has provided evidence to show the claimed method works in the elimination of senescent renal proximal endothelial cells; however, kidney disease is a generic term for heterogenous disorders affecting kidney structure and function, and it is not clear based on the specification or state of the prior art which specific kidney disease may be treated by the claimed method. Applicant’s disclosure is only enabling for the treatment of conditions which Applicant has demonstrated may be treated by the instant compound, and of specific conditions which the art is aware can be treated by elimination of renal proximal endothelial cells for Applicant has written support. Case law is clear on this point. In an unpredictable art, such as drug therapy to treat disease, models may be used for enablement only if there is a well-established correlation between the assay and clinical efficacy. Applicants have not demonstrated nor have they alleged there is any correlation between the in vitro assays they disclose in Figure 13 and clinical efficacy against the entire scope of kidney diseases embraced by the claims. Given the direction provided by Applicant, a person skilled in the art could not practice the full scope of the invention without undue and unreasonable experimentation.
As a general rule, enablement must be commensurate with the scope of claim language.MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification 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, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int'l, Inc. v. BMWofN. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
Nature of the Invention and Breath of the Claims
Claim 1 is drawn to a method of selectively eliminating senescent skin fibroblasts, senescent lung fibroblasts, senescent umbilical vein endothelial cells, and senescent renal proximal tubule endothelial cells comprising administering a composition comprising triacsin C, to treat idiopathic pulmonary fibrosis, osteoarthritis, atherosclerosis, kidney disease, skin wounds, and skin aging in a patient.
Claims 3, 6-8, 10-11, 13, 15 and 23 depend from claim 1 and recite additional limitations to the method including wherein the patient has “kidney disease” (claim 13) or “liver fibrosis” (claim 23).
The nature of the invention is a method of treating disease including kidney disease. The scope of kidney disease is not defined in the specification. The scope of the method therefore broadly includes all conditions embraced by the generic term “kidney disease”.
The state of the prior art
The prior art is aware that kidney disease includes many distinct conditions. Levey et al. (Lancet 2011, Vol 379, 165-180) (hereinafter “Levey”) teaches chronic kidney disease is a general term for heterogeneous disorders affecting the structure and function of the kidney. The variation in disease expression is related partly to cause and pathology, severity, and rate of progression… The definition of chronic kidney disease is based on the presence of kidney damage (ie, albuminuria) or decreased kidney function (ie, glomerular filtration rate [GFR] <60 mL/min per 1·73 m²) for 3 months or more, irrespective of clinical diagnosis (panel 1). Because of the central role of GFR in the pathophysiology of complications, the disease is classified into five stages on the basis of GFR (Introduction). Levey teaches chronic kidney disease is associated with old age, diabetes, hypertension, obesity, and cardiovascular disease, with diabetic glomerulosclerosis and hypertensive nephrosclerosis as
the presumed pathological entities (page 166, causes). Levey further discloses disease management is based on clinical diagnosis and stage according to GFR and albuminuria. Identification of clinical diagnosis allows for specific therapy that is directed at the cause and pathological
processes. Thereafter, disease stage can be used to guide non-specific therapies to slow progression and
reduce the risk of complications (page 169, Management).
Given the varied nature of kidney disease, causes of the condition, and treatment that depends on diagnosis, the state of the prior art does not appear to be aware that a single approach or therapeutic agent treats the entire scope of conditions or stages regarded as “kidney disease”.
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability in the art
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Amount of guidance/working examples
Applicant demonstrates that the instant method results in elimination senescent renal proximal endothelial cells (RPTECs) (Figure 13); however, there is no direction provided regarding which particular kidney disease the instant method treats. There is no evidence of the record, or statement by Applicant, that the elimination of senescent renal proximal endothelial cells is recognized in the prior art as a general strategy for treating kidney disease which the prior art recognizes is highly varied with regard to causes and treatment.
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence 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. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
This conclusion is clearly justified here and one skilled in the art could not practice the full scope of the claimed invention without undue and unreasonable experimentation.
Claim Rejections - 35 USC § 112b
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, 3, 6-8, 10-11, 13, 15 and 23 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. [A] claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear (MPEP 2173.04). The following terms and/or phrases render the scope of the claims unclear because the specification does not provide a scope limiting definition of the phrase or term, or any direction for ascertaining the scope of the limitation indicated by the term or phrase. Accordingly, one skilled in the art could not ascertain the metes and bounds of the claimed invention.
Claims 1 and 13 recite the limitation “kidney disease”. “Kidney disease” is indefinite for the reason that the term is generic and embraces different disorders of the kidney (see State of the Prior Art in the above rejection). The claim would be more clear if amended to recite specific kidney disease or stages of disease which are supported by specification as filed. Claims 3, 6-8, 10-11 and 15 depend from claim 1, fail to clarify “kidney disease”, and are also indefinite.
Claim 15 recites the limitation “patient is at risk of developing scar formation and fibrosis”. This limitation is indefinite because the specification does not teach which particular patients meet this limitation or how to identify patients who are at such a risk. Examiner suggests amending the claim to clarify which patients are intended by the method.
Claim 23 recites the limitation “liver fibrosis”. There is insufficient antecedent basis for this limitation in the claim because claim 23 depends from claim 1 which does not recite treating a condition related to “liver fibrosis”.
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.
Claim(s) 1, 15 and 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Matsuda et al. (J Antibiot. 61(5): 318-321, 2008) (hereinafter “Matsuda”).
Matsuda teaches a method of treating atherosclerosis comprising administration of a composition comprising triacsin C (page 319, Figure 1 and Figure 2; In Vivo Anti-atherosclerotic Activity: triacsin C was administered orally every day for two months). The instant specification does not teach which patients are at risk for developing scar formation and fibrosis. Matsuda is thus regarded as meeting this claim limitation.
The additional claim phrases “selectively eliminating senescent skin fibroblasts, senescent lung fibroblasts, senescent umbilical vein endothelial cells, and senescent renal proximal tubule endothelial cells” and “ wherein senescent cells are characterized by an increased intracellular level of lysophosphatidylcholine, arachidonic acid and/or phospholipase A2 activity compared to a non-senescent cell of the same type or age” appear to be the biological result or consequence of administration of triacsin C. The prior art teaches the claimed method step of administering triacsin C in the treatment of a atherosclerosis and therefore the downstream biological effects that result from this administration would be intrinsic to the prior art method. Providing an explanation for how the prior art method may work is not a limitation which distinguishes the instant method from the prior art.
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.
Claim(s) 1, 3 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matsuda et al. (J Antibiot. 61(5): 318-321, 2008) (hereinafter “Matsuda”) in view of Jawien et al. (European J of Clinical Investigation 2006, 36, 141-146)(hereinafter “Jawien”).
Matsuda teaches a method of treating atherosclerosis comprising administration of a composition comprising triacsin C as discussed in the rejection above, the teachings of which are incorporated herein by reference. Matsuda is silent regarding wherein the composition further comprises MK866; however, Jawien teaches MK866 treats atherosclerosis (Title, Abstract: MK886 reduces development of atherosclerosis in mice).
The claims differ from the prior art by reciting the composition further comprises MK886. However, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the instant application to administer triacsin C and MK886 as a composition in the treatment of atherosclerosis because both compounds were believed to have use in treating the condition.
One would have been motivated as a matter of treating atherosclerosis. The idea of combining the teachings of the references flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
One would have had a reasonable expectation of success because both compounds where known to have use in the treatment of atherosclerosis.
Claim(s) 1, 3 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matsuda et al. (J Antibiot. 61(5): 318-321, 2008) (hereinafter “Matsuda”) in view of Vidal et al. (The Journal of Pharmacology and Experimental Therapeutics 2007, Vol 320, 108-116) (hereinafter “Vidal”).
Matsuda teaches a method of treating atherosclerosis comprising administration of a composition comprising triacsin C as discussed in the rejection above, the teachings of which are incorporated herein by reference. Matsuda is silent regarding wherein the composition further comprises licofelone; however, Vidal teaches licofelone is a treatment atherosclerosis (Title, Abstract). Vidal teaches licofelone has a protective effect on the atherosclerotic process and exerts a beneficial anti-inflammatory effect on atherosclerotic lesions (page 115, col 2).
The claims differ from the prior art by reciting the composition further comprises licofelone. However, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the instant application to administer triacsin C and licofelone as a composition in the treatment of atherosclerosis because both compounds were believed to have use in treating the condition.
One would have been motivated as a matter of treating atherosclerosis. The idea of combining the teachings of the references flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
One would have had a reasonable expectation of success because both compounds where known to have use in the treatment of atherosclerosis.
Allowable Subject Matter
Claims 20-21 and 24-25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The closest reference to the instant claims is Matsuda which was discussed in the rejections herein. Matsuda is silent regarding the treatment of idiopathic pulmonary fibrosis, osteoarthritis, a skin wound or skin aging as recited in the claims. There is no teaching which would have motivated a person of ordinary skill in the art prior to the effective filing date of the instant application to modify Matsuda to treat the claimed conditions with any reasonable expectation of success.
Conclusion
No claim is allowed.
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October 22, 2025
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624