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 .
Claims 1 and 7 have undergone amendments and claims 6 and 9 have been cancelled. Thus, Claims 1-5 and 7-8, submitted on 29 October 2025, represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 29 October 2025 is acknowledged and has been considered.
Response to Amendment
The objection to the specification is withdrawn. Applicant has amended the specification to provide proper symbols indicating use in commerce.
The objection to the drawings are withdrawn. Applicant has attached replacement sheets which provide clear figures.
The objection to Claim 9 is withdrawn. Applicant has cancelled claim 9, rendering the objection moot.
The 35 U.S.C. § 112(a) rejection of Claim 9 is withdrawn. Applicant has cancelled Claim 9, rendering the rejection moot.
The 35 U.S.C § 112(b) rejection of Claims 1-9 is withdrawn. Applicant has amended Claim 1 to remove the limitation of “including but not limited to”.
The 35 U.S.C. § 112(b) rejection of Claims 1-4 and 6 is withdrawn. Applicant has amended the Claim 1 to remove “lower alkyl, lower alkenyl, or lower alkynyl”.
The 35 U.S.C. § 112(b) rejection of Claim 7 is withdrawn. Applicant has amended Claim 7 to indicate that variable R3 is -OH, not both -H and -OH.
The 35 U.S.C. § 112(b) rejections of Claim 9 are withdrawn. Applicant has cancelled the claim, rendering the rejections moot.
The 35 U.S.C. § 102(a)(1) rejection of Claims 1, 2, and 6 over Kang is withdrawn. Applicant has amended the structure of Formula II to not encompass caffeic acid.
The 35 U.S.C. § 102(a)(1) rejection of Claims 1, 3, and 6 over Joshi is withdrawn. Applicant has amended the structure of Formula II to not encompass caffeic acid.
The 35 U.S.C. § 102(a)(1) rejection of Claims 1, 2, and 6 over Sheng is withdrawn. Applicant has amended the structure of Formula II to not encompass ethyl caffeate, caffeic acid methyl ester, or caffeic acid.
The 35 U.S.C. § 103 rejection of Claims 1-9 over Gomes in view of Etzenhouser and Kang is withdrawn. Applicant has amended Claim 1 to specify a dosage, which was not claimed in the prior claim set. However, a new ground of rejection is made over Gomes in view of Kang and Loftsson (Essential Pharmacokinetics, Chapter 5-Pharmacologic Response and Drug Dosage Adjustments, Pages 119-130, Volume 1, 2015).
The 35 U.S.C § 103 rejection of Claims 1-3, 6, and 9 over Paul in view of Kang is withdrawn. Applicant has amended Claim 1 to remove alkyl chains from variable R1, and a double bond from variable R8 and R9.
Claim Rejections - 35 USC § 103- NEW GROUNDS OF REJECTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Gomes (J. Med. Chem, 2003, 46, 5395-5401) in view of Kang (Carcinogenesis, Vol 3, Issue 2, February 2009, Pages 321-330) and Loftsson (Essential Pharmacokinetics, Chapter 5-Pharmacologic Response and Drug Dosage Adjustments, Pages 119-130, Volume 1, 2015).
Gomes (See IDS, 11 October 2022) synthesized caffeic acid derivatives and screened them for potential antiproliferative and cytotoxic properties in different human cancer cell lines- mammary gland and cervix adenocarcinomas and lymphoblastic leukemia (Abstract). Among the compounds which were synthesized and tested were 3-4 dihydroxyphenylethanoic acid (DHPE) and hydrocaffeic acid (3,4-dihydroxyhydrocinnamic acid) (Page 5396). DHPE
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has variables R3 and R4 as -OH, variable Z as 1, variables R1, R2,R5, R6, R8, and R9 as H, and variable X as O, meeting the limitations of Claims 1, 2, and 6. DHPE displayed a specific and almost irreversible antiproliferative and cytotoxic effects on MOLT-3 cells, with cell viability reduced to approximately 75% after 72h of incubation at concentrations of 50µM. Hydrocaffeic acid
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has variables R4 and R5 as hydrogen, variable z as 2 with variables R8 and R9 as hydrogen, and variable X as oxygen. This compound is identical to the compound of Claim 8 of the examined application. This phenolic acid was found to have an irreversible antiproliferative activity against all cell lines studied (Figure 5), along with a rather modest cytotoxic effect (Figure 2). This compound displayed a clear specificity against the adenocarcinoma cell lines tested, mainly toward HeLa (Figure 5). An increase in the number of OH ring substituents in the compounds investigated leads to higher antiproliferative and cytotoxic activities in all cell lines tested (Figures 2 and 3). It was observed for all cell lines tested that the presence of a double bond is associated with an increase in cell viability compared to the saturated compounds (Figure 4).
Gomes does not teach the inhibition of Src kinases.
Kang teaches the use of caffeic acid
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for the inhibition of the Src kinase Fyn. Caffeic acid haz variables R3 and R4 as -OH, X as O, a single alkenyl group present, and hydrogens for R2, R5, and R6, differing from the compounds of the examined application by the presence of an unsaturated bond. Kang found that Fyn, one of the members of the non-receptor protein tyrosine kinase family, was required for UVB-induced COX-2 expression, and caffeic acid suppressed UVB-induced skin carcinogenesis by inhibiting Fyn activity (Abstract).
Gomes and Kang do not teach the claimed dosage range of 0.1 mg/day to 1g/day.
Loftsson teaches dosing of pharmaceuticals and that drugs are administered on the basis of their average pharmacokinetic parameters in normal patient populations (Page 119). Many drugs have wide therapeutic windows and can easily remain within this window (Page 119). Pharmacodynamics describes the relationship between drug concentration at the receptor and the drug effect, with the receptor being a well-defined place in the body, or it can be on or within the surface of a microorganism within the body (Section 5.3, Pharmacodynamics). The relationship between drug concentration and drug effect is shown in Figure 5.2A; at high drug concentrations, the drug effect approaches a maximum value where 100% drug response is obtained. At this concentration, virtually all receptors/drug targets have formed a drug-target complex. This relationship is sigmoidal (Section 5.3, Pharmacodynamics).
Gomes, Kang, and Loftsson are considered analogous to the claimed invention as all are involved in the development and use of drugs or drug-like compounds for the treatment of disease. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to utilize the compounds of Gomes for the inhibition of Src kinase at the claimed dosages to arrive at the claimed invention. This combination of teachings to arrive at the claimed invention is prima facie obvious combining of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)), wherein the known elements are the anti-cancer activity of hydrocaffeic acid, taught by Gomes, used to inhibit Src kinases as taught by Kang. Hydrocaffeic acid differs from caffeic acid by the presence of a double bond, and due to the structural similarity, the artisan would not expect these compounds to have significantly different biological properties (See MPEP § 2144.09 I) as hydrocaffeic acid is similarly capable of killing leukemia cells. Regarding the claimed dosage, Gomes demonstrates that these compounds have in vitro activity against cancer cells, and the artisan, a trained medical professional, would have an understanding of pharmacokinetics and pharmacodynamics, and would understand how to properly dose the claimed compounds in order to be dosed within its therapeutic window using the data from Gomes as a guide. Dosage adjustments, such as increasing the dosage or time period of treatment, is prima facie obvious optimization within prior art conditions (See MPEP § 2144 II (A)).
Regarding Claims 2-5, these compounds are structural isomers of hydrocaffeic acid, with the hydroxyl groups moved to different positions around the phenyl ring. As such, these compounds are prima facie obvious due to the close structural similarity to hydrocaffeic acid, which Gomes demonstrates possesses anti-cancer properties and as such, the artisan would not expect these compounds to have significantly different biological properties as they are structural isomers of one another (See MPEP § 2144.09 I).
Conclusion
Claims 1-5 and 7-8 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625