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 .
Status of the Claims
The amendments and arguments filed 02/11/2026 are acknowledged and have been fully considered. Claims 5-8 and 11 are now pending. Claims 1-4 and 9-10 are cancelled; claims 5-8 and 11 are amended; no claims are withdrawn; no claims are new.
Claims 5-8 and 11 will be examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 5 is objected to because of the following informalities: the claim recites “a preparation method for a micelle, wherein the micelle comprises a the paclitaxel prodrug…” (emphasis added). Here, the articles “a” and “the” used sequentially is improper grammar and suggests that the claim may improperly rely on antecedent basis for a paclitaxel prodrug recited in a canceled claim. Moreover, the claim includes the term “praclitaxel,” which is not an art-recognized term or a term defined in the disclosure. Appropriate correction is required. It is advised that Applicant remove the word “the” from the claim. It is advised that Applicant amend the term “praclitaxel” to “paclitaxel.”
Claim 11 objected to because of the following informalities: the claim recites “the method of claim for use,” which lacks the claim number for the claim being referenced. It is advised that Applicant add the number of the claim which Applicant intends to incorporate the limitations of. Appropriate correction is required.
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.
Claim 11 is 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.
Claim 11 recites the limitation “the micelle prepared according to the method of claim for use in the preparation of medicaments for treating cancers.” Here, the phrase “the method of claim” does not point to a particular claim, and the method therefore lacks antecedent basis for the claim referenced. In other words, it does not point out which claim limitations from the prior claims are incorporated into claim 11. As such, the term “the method” lacks antecedent basis, as it is not clear which method is referenced. Here, there is insufficient antecedent basis for this limitation in the claim. Here, for the purposes of examination, the claim will be interpreted as follows: the micelle prepared according to the method of claim 5 for use in the preparation of medicaments for treating cancers.
Claim Rejections - 35 USC § 102
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 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 5-8 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (Wu, HC. et al. Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme. Chin J Polym Sci 40, 491-503 (2022)).
With regard to claim 5, Wu et al. teach a preparation method for a micelle, wherein the micelle comprises a paclitaxel prodrug, the method comprising the following steps: (1) Paclitaxel reacts with dithiopropionic acid anhydride (DTDPA or DTPA) in the organic solvent tetrahydrofuran (THF) in the presence of the activator 4-dimethylaminopuridine (DMAP) and the stabilizer hydroxybenzotriazole (HOBT) to yield PTX-ss (i.e. PTX-DTPA, see Figure 1) (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD and page 495 Figure 1); (2) PTX-DTPA reacts with NH2-PEG-Mal (i.e. Maleimide-PEG-Amine, see page 492 Methods and page 494 Chemical Composition and Structure) in an organic solvent, THF, in the presence of activator N-hydroxysuccinimide (NHS), the stabilizer HOBT, and the condensation agent dicyclohexyl carbodiimide (DCC) to yield PTX-DTPA-PEG (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD); (3) PTX-DTPA-PEG and the cyclic peptide RGDfC react in aqueous solvents, PBS, to prepare the paclitaxel prodrug (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD), which yields the following:
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1H NMR spectra of PTX-ss-PEG-c(RGDfC) (see Wu et al. Electronic Supplementary Information Figure 2); and (4) dissolving the PTX-polymer-drug conjugates (PTX-PDCs) in an organic solvent, 1 mL of THF, then adding the mixture dropwise into 10 mL of distilled deionized water with stirring, and finally evaporating the micellar solution to remove the THF and obtain the product, which is referred to as micelles (see pages 492, 493 Preparation of PTX-PDCs NPs and Scaffolds, 497 In Vitro Drug Release, and Table 1).
With regard to claim 6, Wu et al. teach the preparation method discussed above characterized in that the reaction of step (1) used DMAP, HOBT, and THF, the reaction of step (2) uses NHS and HOBT, and the reaction of step (3) uses PBS as the aqueous solution (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD). Although Wu et al. do not teach the use of the dichloromethane in step (2), the use of the language “and/or” renders the claim limitation met if any of the steps of S1, S2, and/or S3 are taught. Here, the limitations of S1 and S3 are taught by Wu et al.
With regard to claim 7, Wu et al. teach the preparation method discussed above characterized in that the reaction in step (1) is carried out at room temperature, which is known in the art as being about 20-25°C for 24 hours (see Wu et al. Synthesis of PTX-ss-PEG-RGD). The reaction in step (2) is performed as follows: PTX-DTPA is mixed with the condensation agent, activator, and stabilizer in an ice bath, which is known in the art as being about 0°C (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD). The mixture is allowed to react for 6 hours, and then NH2-PEG-Mal is added and the mixture is stirred for 24 hours at room temperature (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD). The reaction in step (3) is carried out at room temperature for 24 hours (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD).
With regard to claim 8, the preparation method of Wu et al. discussed above is characterized in that step (2) has a molar ratio of 1:0.75:3:3:3 for PTX-DPTA, NH2-PEG-Mal, NHS, HOBT, and DCC, respectively (see Wu et a. page 492 Synthesis of PTX-ss-PEG-RGD). Moreover, the molar ratio for step (3) is 5:4 for PTX-DTPA-PEG and cyclic RGDfC, respectively (see Wu et a. page 492 Synthesis of PTX-ss-PEG-RGD).
With regard to claim 11, Wu et al. teach the nanoparticle drug-loaded microspheres for use in the preparation of medicaments for treating cancers like Glioblastoma multiforme (see page 491 Abstract). The resultant structures of the PTX-ss-PEG-RGDfC nanoparticles are referred to as micelles explicitly (see page 497 In Vitro Drug Release and Table 1). Further, unless an unobvious structural limitation is provided by the process limitation, patentability of product-by-process claims are based on the product itself (see MPEP 2113). As in Wu et al., the teachings of the prior art appear to meet the limitations recited in the instant claim. “The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature” than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983), emphasis added. Here, seeing as the claim is a product-by-process claim, a claim whereby the product is claimed as the product of a process, the patentability of a product does not depend on its method of production. In this case, the disclosure does not teach that the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product or that the product can only be defined by the process steps by which the product is made. As taught by Wu et al., the product in the product-by-process claim is the same as or obvious from a product of the prior art, and the claim is therefore unpatentable even though the prior product was made by a different process. Moreover, both products have the same intended use as a cancer treatment. Specifically, Wu et al. teach treating glioblastoma multiforme (see Abstract). Given that the prior art teaches the same structure for the same intended function, the invention of Wu et al. is capable of the intended use of the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 5-8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Wu, HC. et al. Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme. Chin J Polym Sci 40, 491-503 (2022)) as applied to claims 5-8 and 11 above, and further in view of Jandeleit et al. (US Patent No. 9,783,487).
As discussed above, Wu et al. teach a paclitaxel prodrug characterized in that its structure comprises a disulfide bond, a polyethylene glycol molecular chain, and an RGD peptide chain (see page 492 Synthesis of PTX-ss-PEG-RGD and page 491 Abstract). Paclitaxel is known to have good therapeutic effects on ovarian cancer, breast cancer, prostate cancer, lung cancer, and more. The paclitaxel prodrug of Wu et al. is created by the following process: (1) Paclitaxel reacts with DTPA in the organic solvent THF in the presence of the activator DMAP and the stabilizer HOBT to yield PTX-DTPA (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD and page 495 Figure 1); (2) PTX-DTPA reacts with NH₂-PEG-Mal in an organic solvent, THF, in the presence of the activator NHS, the stabilizer HOBT, and the condensation agent DCC to yield PTX-DTPA-PEG (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD); and (3) PTX- DTPA-PEG and the cyclic peptide RGDfC react in aqueous solvents, PBS, to prepare the paclitaxel prodrug (see Wu et al. page 492 Synthesis of PTX-ss-PEG-RGD).
Although this method closely matches the method of the instant application, Wu et al. do not explicitly teach the use of dichloromethane (DCM) as the organic solvent for step (2) of this reaction. The use of DCM as the organic solvent in step (2) of this reaction does not have to be taught by a reference in order to reject claim 6 because of the use of the term "and/or" in this claim limitation. The claim has already been rejected under 35 U.S.C. 102(a)(1) as discussed above, and the following argument is provided for the purpose of compact prosecution.
Jandeleit et al. teach methods for creating chemotherapy drugs to treat cancers including lung, breast, prostate, and ovarian. Specifically, Jandeleit et al. teach methods for making amino acid derivatives and analogs that serve as therapeutics. Jandeleit et al. use methods adapted from the literature to synthesize the amino acid compounds for use in targeting cancer. Namely, Jandeleit et al. teach the use of DCM as the organic solvent for this step of the reaction in combination with the drug precursor, DCC, NHS, and HOBT (see [1010]).
Regarding claim 6, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Wu et al. to use DCM as the organic solvent for step (2) as taught by Jandeleit et al. to synthesize the chemotherapy. One would be motivated to use the method of Jandeleit et al., specifically the DCM solvent, to synthesize the drug of Wu et al. with a reasonable expectation of success because they are both amino acid-containing chemotherapies that treat overlapping types of cancers. Further, the instant case is substituting one known method for another to yield predictable results. Namely, the instant application applies the known method of Jandeleit et al. in using DCM as the organic solvent rather than THF when reacting drug precursors with DCC, HOBT, and NHS to make the target drug compound. As such, the instant case simply applies one known technique that uses the DCM solvent instead of THF to synthesize the same drug taught in Wu et al. Given this, a skilled artisan would have been motivated to use DCM instead of THF to synthesize the Paclitaxel drug.
Claims 5-8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Wu, HC. et al. Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme. Chin J Polym Sci 40, 491-503 (2022)) as applied to claims 5-8 and 11 above.
With regard to claim 8, as discussed above, the preparation method of Wu et al. is characterized in that step (2) has a molar ratio of 1:0.75:3:3:3 for PTX-DPTA, NH2-PEG-Mal, NHS, HOBT, and DCC, respectively (see Wu et a. page 492 Synthesis of PTX-ss-PEG-RGD). Moreover, the molar ratio for step (3) is 5:4 for PTX-DTPA-PEG and cyclic RGDfC, respectively (see Wu et a. page 492 Synthesis of PTX-ss-PEG-RGD).
Wu et al. do not, however, teach that the molar ratio of PTX, DTPA, the activator, and the stabilizer in step (1) is 2:1:0.06:0.06. Rather, Wu et al. teach a molar ratio similar to that used in the specification of the instant application, 1:1:2:2. The use of a 2:1:0.06:0.06 molar in step (1) of this reaction does not have to be taught by a reference in order to reject claim 8 because of the use of the term "and/or" in this claim limitation. The claim has already been rejected under 35 U.S.C. 102(a)(1) as discussed above, and the following argument is provided for the purpose of compact prosecution.
According to relevant case law, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America V. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.") In the instant case, Wu et al. and the Applicant use different starting molar ratios for the reaction steps, but in subsequent steps, the ratios are identical. This suggests that it is possible to use different starting values to yield the same relative amount of a final product. These claimed amounts are therefore close because they demonstrate the same properties insofar as they yield the same amount of product. As such, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Wu et al. to use different starting molar ratios, seeing as it would yield the same relative amount of product.
Response to Arguments
Applicant's arguments filed 02/11/2026 have been fully considered but they are not persuasive. Applicant argues that claim 5 is not anticipated at least because Wu et al. and Jandeleit et al. do not disclose the step of S4, which was introduced in the amendment filed 02/11/26. This amendment has support in the original disclosure, but it is still anticipated by Wu et al. As discussed above, Wu et al. teach dissolving the PTX-polymer-drug conjugates (PTX-PDCs) in an organic solvent, 1 mL of THF, then adding the mixture dropwise into 10 mL of distilled deionized water with stirring, and finally evaporating the micellar solution to remove the THF and obtain the product, which is referred to as micelles (see pages 492, 493 Preparation of PTX-PDCs NPs and Scaffolds, 497 In Vitro Drug Release, and Table 1). For this reason, the argument is not persuasive, as the amended limitation is anticipated by Wu et al.
Summary
Claims 5 and 11 are objected to on the grounds of informalities. Claim 11 is rejected under 35 U.S.C. 112(b) on the grounds of lack of antecedent basis. Claims 5-8 and 11 are rejected under 35 U.S.C. 102(a)(1) on the grounds of anticipation. Claims 5-8 and 11 are rejected under 35 U.S.C. 103 on the grounds of obviousness.
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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brendan P Oliss whose telephone number is (571)272-6347. The examiner can normally be reached Monday - Thursday 8 am - 6 pm.
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658