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 .
1. Claims 2-5, 9-12, and 17-20 have been cancelled. Claims 1, 6, and 13 have been amended.
Claims 1, 6-8, and 13-16 are pending and under examination.
2. All rejections/objections pertaining to claims 2-5, 9-12, and 17-20 are moot because the claims were cancelled with the reply filed on 05/12/2026.
The objection to claim 1 is withdrawn in response to the amendment filed on 05/12/2026.
The rejection of claim 13 under 35 U.S.C. 112(b) is withdrawn in response to the amendment to correct for antecedent basis.
The following rejections are withdrawn in response to the amendment to introduce the limitations of the cancelled claims into the independent claim 1:
The rejection of claims 1, 2, 6-8, 12, and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Zhou et al. (Materials Letters, 2018, 221: 131-134);
The rejection of claims 1-3, 5-9, 11-17, 19, and 20 under 35 U.S.C. 103 as being unpatentable over Zhou et al., in view of Choi et al. (Biomaterials, 2012, 33: 4195-4203).
New grounds of rejection are set forth below.
Claim Objections
3. Claims 15 is objected to because of the recitation “the drug is loaded in the nanoparticle, the nanoparticle is a liposome”. Correction to “the drug is loaded in the liposome” is required.
Claim Rejections - 35 USC § 112(b)
4. 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.
5. Claims 8 and 16 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 8 and 16 are indefinite as being both incomplete, by their dependence on a cancelled claim; and for lack of antecedent basis for their limitation which is not present in the cancelled base claim.
Claim Rejections - 35 USC § 103
6. 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.
7. Claims 1, 6-8, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Materials Letters, 2018, 221: 131-134), in view of both Choi et al. (Biomaterials, 2012, 33: 4195-4203) and Sun et al. (Chem. Commun., 2016, 52: 4602-4612).
Zhou et al. teach a mesenchymal stem cell (MSC) comprising on its surface cyclodextrin (CD) attached via DSPE-PEG and azobenzene-modified nanoparticles (Azo-NPs) bound to the MSC surface via host-guest interactions between βCD and Azo. Thus, Zhou et al. teach a supramolecular cell-based carrier (claims 1 and 6). Zhou et al. teach obtaining the carrier by: (1) coupling βCD to the PEG moiety of DSPE-PEG to obtain DSPE-PEG-CD; (2) incubating the MSCs with DSPE-PEG-CD for 30 min at
37 ºC to obtain βCD-modified MSCs; and (3) mixing the βCD-modified MSCs with the Azo-NPs for 30 min (claims 6-8, 13, and 14) (see Abstract; p. 131-132; p. 133; p. 134, column 1; Supplemental Material, third page).
Zhou et al. teach an MSC, not a macrophage (claim 1). Although Zhou et al. teach choosing MSCs because of their ability to target tumors, Zhou et al. teach that macrophages are also suitable to be used as vehicles for nanoparticle-based DDS (see p. 131, column 1; p. 134, column 1, last paragraph). Furthermore, Zhou et al. teach that the supramolecular cell-based carrier is suitable for targeted drug delivery (see p. 134, column 1 last paragraph). Choi et al. teach that macrophages are capable of targeted drug delivery to tumors due to their ability to home to tumors; Choi et al. teach using macrophages for the delivery of liposomal doxorubicin (LP-Dox) to the tumors of a subject affected by cancer (see Abstract; p. 4196, column 1, last three paragraphs; last paragraph). Based on these teachings, one of skill in the art would have found obvious to modify Zhou et al. by replacing the MSC with a macrophage to achieve the predictable result of obtaining a composition capable of delivering therapeutic agents to tumors. One of skill in the art would have also found obvious to further modify the LP-Dox of Choi et al. with Azo and either attach the resultant Azo-LP-Dox to the macrophage via the host-guest interactions alongside Azo-NPs or replace the Azo-NPs with Azo-LP-Dox, with the reasonable expectation that doing so would result in a composition suitable to be used in cancer therapy (claim 1). By doing so, one of skill in the art would have obtained a drug carrying system as recited in claims 15 and 16.
Zhou et al. teach incubating for 30 min, not for more than 30 min as recited in claim 13. However, MPEP 2144.05 III A states that "[a] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In this case, there is no evidence of a difference in kind or even degree when using an incubation time of more than 30 min instead of 30 min.
With respect to the DSPE-PEG-CD concentration range (claim 13), there is no evidence of record indicating that using the claimed 1 µM-1 mM range leads to unexpected results. One of skill in the art would have reasonably concluded that DSPE-PEG-CD concentration is a result effective variable with respect to Dox loading (and thus, therapy) and would have found obvious to optimize the composition for therapeutic effectiveness via varying the amount of DSPE-PEG-CD, which would have only entailed routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed range was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
Zhou et al. and Choi et al. do not teach adamantane (ADA) (claim 1). However, it was known in the prior art that ADA and Azo are functional equivalents with respect to interacting with CD (see Sun et al., p. 4603, column 2, first full paragraph; p. 4606, column 2, last paragraph; p. 4607, paragraph bridging columns 1 and 2; p. 4608). One of skill in the art would have found obvious to replace Azo with ADA to achieve the predictable result of obtaining a supramolecular cell-based carrier.
With respect to the molar ratio range recited in claim 1, there is no evidence of record indicating that using the claimed range leads to unexpected results. One of skill in the art would have reasonably concluded that the ratio is a result effective variable with respect to Dox loading (and thus, therapy) and would have found obvious to optimize the composition for therapeutic effectiveness via varying the ratio between CD and ADA, which would have only entailed routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed range was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
With respect to the range of ≥10 sec recited in claim 14, Zhou teaches 30 min when using βCD/Azo, which falls within the claimed range. Furthermore, since Sun et al. teach that βCDs and ADA form inclusion complexes with high association constants the range of 104-105 (see p. 4608), one of skill in the art would have found obvious to vary the time, with the reasonable expectation that doing so would identify the optimal conditions for obtaining the βCDs/adamantane inclusion complexes.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
8. The argument addressing Choi are not found persuasive. The rejection is not based on partially applying Choi’s technique to Zhou. The rejection is based on modifying Zhou by replacing one cell type with another; and by replacing the nanoparticle with LP-Dox. This would have only entailed routine experimentation and would have not changed the mode of action in Zhou.
This following arguments are not found persuasive because they are just arguments not supported by any evidence: (1) based on Sun, the effect of adamantane cannot be known without a doubt when used with macrophages and liposomes; (2) the selection of the claimed combination is not routine.
With respect to the argument that adamantane and cyclodextrin form a stable host-guest interaction, this was reasonably expected from Sun’s teaching that adamantane and cyclodextrin attach via strong interactions.
The applicant argues that the molar ratio does not constitute routine experimental optimization.
This is not found persuasive for the reasons set forth in the rejection. It is also noted that claim 1 (reciting the ratio) is a composition, not a method claim. The argument that the recited molar ratios significantly reduce the preparation time is not material to a composition claim because a shorter time does not change the composition structure as compared to the prior art. The specification does not provide any evidence to this effect.
With respect to the method claims, they are not limited to 1-5 min incubation. And even assuming that the method claims would be limited to 1-5 min incubation, as per MPEP 2144.05 III A: "[a] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In this case, there is no evidence of a difference in kind or even degree when using 1-5 min instead of 30 min. Furthermore, it is noted that Examples 1-5 and 8 (only disclosing a molar ratio of 1:1) do not even demonstrate criticality for the specific 1:1 ratio or the 1:10 to 10:1 ratio range with respect to shortening the incubation time.
Conclusion
9. 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.
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/ILEANA POPA/ Primary Examiner, Art Unit 1633
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