Detailed Action
The present office action is in response to the remarks filed on 02 Apr 2026.
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 .
Status
Claims 1-5, 7-8, and 15-18 of the pending application have been examined on the merits. Claims 9-10 and 19-20 remain withdrawn. Acknowledgement is made of the amendments filed 02 Apr 2026. Acknowledgement is made of the cancellation of claims 6 and 11-14.
Priority
The instant application retains the priority date of 17 Dec 2019.
Response to Applicant Remarks
Acknowledgement is made of applicant remarks filed 02 Apr 2026.
The objection to claims 1 and 3-4 are rendered moot following applicant amendments.
The rejections of claims 6 and 11-14 are rendered moot following applicant cancellation of the claims.
The rejection of claims 1-5, 7-8, and 15-18 under 35 U.S.C. § 101 are rendered moot following applicant amendments.
The rejection of claims 1-5, 7-8, and 15-18 under 35 U.S.C. § 112(b) are rendered moot following applicant amendments.
The rejection of claim 2 under 35 U.S.C. § 112(d) is rendered moot following applicant amendments.
The rejection of claims 1-5, 7-8, and 15-18 under 35 U.S.C. § 102(a)(1) over CN 110721185 (provided in the office action mailed 02/20/26), hereinafter ‘185, is rendered moot following applicant amendments. However, after a further search, a new grounds of rejection is made in view of ‘185 and Du et al. (J Am Chem Soc, 2011, 133:17560-17563), hereinafter Du. This rejection is necessitated by applicant amendments.
The rejection of claims 1-5, 8, and 15-18 under 35 U.S.C. § 102(a)(1) over US 2007/0292433 (provided in the office action mailed 02/20/26), hereinafter ‘433, is rendered moot following applicant amendments. However, after a further search, a new grounds of rejection is made in view of ‘433 further in view of Du. This rejection is necessitated by applicant amendments.
Applicant arguments regarding the unexpected results in the remarks filed 02 Apr 2026 have been fully considered but are not persuasive. Applicant argues that the specification states that the elected Compound 7 (below) is more hydrophobic than the other compounds and can be easily taken up by tumor cells and thus has better therapeutic effects (Remarks, pg. 15).
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This is not persuasive. Arguments presented cannot take the place of evidence in the record. The specification provides no evidence that Compound 7 has better therapeutic effect because it is taken up easier by tumor cells compared to other compounds. See MPEP § 2145(I).
Applicant argues that the combination of Compound 7 decreases PD-L1 expression in a concentration dependent manner and that in combination with doxorubicin, Compound 7 causes tumor cells to express more calreticulin demonstrating that the combination modulates tumor-relevant biological pathways in a manner not suggested by the prior art (Remarks, pg. 16).
This is not persuasive. As stated in the office action mailed 20 Feb 2026, when the prior art teaches the same steps of applying Compound 7 and doxorubicin to cancer cells as found in the instant claims, the outcomes will necessarily be the same. See MPEP § 2112(I).
Applicant further argues that the sensitization of the tumor cells by the combination of Compound 7 and doxorubicin has unexpected superiority to doxorubicin alone. The argument further extends to multiple other cell lines and antitumor molecules and that the person of ordinary skill in the art would not have reasonably expected a sensitizer to produce such broad, cross-drug, and cross cell line enhancement (Remarks, pg. 16)
This is not persuasive. Applicant points to Tables 1 and 2 (pgs. 51-52 of the instant specification) to show the effects of combining Compound 7 with various antitumor agents across cell lines. However, it is unclear whether the effects are additive or synergistic. The experiments do not have the proper controls to make the determination if the results are truly unexpected. The artisan would have expected an additive effect, but not a synergistic effect. Thus the experiments would be unconvincing to the artisan that the addition of Compound 7 to various antitumor compounds creates unexpected results.
Applicant finally argues that Compound 7 and doxorubicin have significant anticancer activity than either agent alone and the tumors did not grow after drug withdrawal and remained unchanged. Applicant argues Compound 7 increases tumor inhibition rates of antitumor drugs by 30-70% and that tumors in the combination group of Compound 7 and doxorubicin liposome were eliminated whereas tumors treated with doxorubicin liposome alone continued to grow (Remarks, pg. 17).
This is not persuasive. It is unclear where the specification provides each claim as argued. However, the experimental data lack analysis showing a synergistic effect. Without further experimental detail, the arguments presented are not persuasive. See MPEP § 2145(I).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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) 1-5, 7-8, and 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over ‘185 and Du.
Applicant elected group I, claims 1-5, 7-8, and 15-18. Applicant further elected Compound 7 as the species of formula (I) and doxorubicin as an antitumor drug. These species read on claims 1-5, 7-8, and 15-18. The claims further limit the mass ratio of antitumor drug sensitizer to antitumor drug to (0.1-20):1 (claim 7).
‘185 teaches using roxadustat to treat doxorubicin cardiomyopathy (pg. 3). ‘185 teaches that roxadustat has the following molecular formula (pg. 2):
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‘185 teaches treatment of two cancer cell lines (HepG2 cells and MCF7 cells) with 5 µM of roxadustat and 1-2 µM of doxorubicin (pg. 5). ‘185 teaches treating mice with 10 mg/kg/day of roxadustat and 12.5 mg/kg/day of doxorubicin dissolved in normal saline, a pharmaceutically acceptable carrier (pg. 3; pg. 4). However, ‘185 does not teach administration of a doxorubicin liposome.
Du teaches that environment-responsive delivery systems have been attempted to improve drug bioavailability and pH-responsiveness is the most frequently used (pg. 17560, column 1). These delivery vehicles can precisely target a tumor environment which has a lower pH than blood and normal tissues (pg. 17560, column 1). Du teaches a dual pH-sensitive polymer-doxorubicin conjugate as a nanoparticulate drug delivery system comprising a parental deblock copolymer monomethoxyl poly(ethylene glycol)-b-poly(allyl ethylene phosphate) conjugated to a doxorubicin (pg. 17560, column 2 to pg. 17561, column 1). Du teaches these doxorubicin nanoparticles can reduce premature drug release during circulation and specifically enhance intracellular drug release which will be beneficial to effective cancer treatment (pg. 17561, column 2).
Based on the teachings of ‘185 and Du, a person of ordinary skill in the art would replace doxorubicin, taught by ‘185, with the doxorubicin nanoparticle taught by Du, and have a reasonable expectation of success that the doxorubicin nanoparticle will retain the antitumor effect of doxorubicin. The artisan would be motivated to make this swap because doxorubicin nanoparticles have can reduce premature drug release during circulation and enhance intracellular drug release, as taught by Du.
By teaching the same steps of applying roxadustat and doxorubicin nanoparticles to cancer cells as found in the instant claims, ‘185 and Du necessarily teach the same outcomes and roxadustat would necessarily act as a sensitizer for an anticancer compound. See MPEP § 2112(I).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-5, 8, and 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over ‘433, further in view of Du.
‘433 teaches Compound D is used to treat chemotherapy induced anemia (paragraph [0235]; paragraph [0312]). Compound D is an alias of the instantly elected Compound 7 (see below).
Compound D
[(4-Hydroxy-1-methyl-7-phenoxy-isoquino line-3-carbonyl)-amino]-acetic acid
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‘433 teaches doxorubicin as one of the possible chemotherapeutics that cause anemia which can be treated with roxadustat (paragraph [0007]; paragraph [0036]; claim 7). ‘433 also teaches suitable carriers for the administration of the reference compounds (paragraph [0300]). However, ‘433 does not teach a doxorubicin liposome.
Du teaches that environment-responsive delivery systems have been attempted to improve drug bioavailability and pH-responsiveness is the most frequently used (pg. 17560, column 1). These delivery vehicles can precisely target a tumor environment which has a lower pH than blood and normal tissues (pg. 17560, column 1). Du teaches a dual pH-sensitive polymer-doxorubicin conjugate as a nanoparticulate drug delivery system comprising a parental deblock copolymer monomethoxyl poly(ethylene glycol)-b-poly(allyl ethylene phosphate) conjugated to a doxorubicin (pg. 17560, column 2 to pg. 17561, column 1). Du teaches these doxorubicin nanoparticles can reduce premature drug release during circulation and specifically enhance intracellular drug release which will be beneficial to effective cancer treatment (pg. 17561, column 2).
Based on the teachings of ‘433 and Du, a person of ordinary skill in the art would replace doxorubicin, taught by ‘433, with the doxorubicin nanoparticle taught by Du, and have a reasonable expectation of success that the doxorubicin nanoparticle will retain the antitumor effect of doxorubicin. The artisan would be motivated to make this swap because doxorubicin nanoparticles have can reduce premature drug release during circulation and enhance intracellular drug release, as taught by Du.
By teaching the same steps of applying roxadustat and doxorubicin to cancer cells as found in the instant claims, ‘433 necessarily teaches the same outcomes and roxadustat would necessarily act as a sensitizer for an anticancer compound. See MPEP § 2112(I).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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