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 .
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.
Claims 2, 5, 6, 8, and 13-17 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.
Range within range rejections:
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “between 20-80kDa”, and the claim also recites “more preferably 40-60 kDa” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 5 recites “and one compound selected form the group consisting of doxorubicin (DOX), ketoprofen (KETO0 and 4-hydroxybenzayl alcohol (HBA)”, but also recites the narrower “more preferably DOX”.
Claim 8 recites the size of the nanoparticles “is at most 260nm”, then recites the narrower “preferably 50 nm to 260 nm”.
Claim 13 recites “one compound selected from the group consisting of DOX, KETO and HBA”, but also recites the narrower “more preferably DOX.”
Claim 15 recites in step i, “1 to 60 molar%”, but also recites the narrower “preferably 3 to 55 molar%, in particular e.g. 3.4 to 53.8 molar%”.
Claim 16 recites coupling reaction agents, but also recites the narrower “more preferably EDC” and also recites catalysts, but also recites the narrower “more preferably without catalyst in case of EDC”.
Indefinite terms rejections:
Claim 6 and 14 recite “when the carboxylic content is approx. 9% by weight.” It is unclear if this is a required limitation (i.e. the formulation has to have a carboxylic content of approximately 9% by weight) or a conditional limitation which may define the rest of the claim only when the carboxylic content is at the defined amount.
Claim 15, step vi, recites “preferably in approx. 50 mol% excess”. Given the modifier “preferably”, it is unclear if this is a required element or just an optional element. Applicants use the term optionally throughout the process claim, so it is unclear how preferably and optionally differ.
Lack of antecedent basis rejections:
Claim 6 and 14 recite “3.3% and 6.2% by weight of the formulation, respectively”, lacks antecedent basis where the claims are directed to a mucoadhesive polymeric prodrug, not a “formulation”. This is further confused by the limitations following which discusses the total amount of the polymeric prodrug.
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 1-14 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Stipniece et al (Journal of Crystal Growth, 444 (2016) 14-20) in view of Qavamnia et al (Incorporation of Hydroxyapatite/Doxorubicin into the Chitosan/Polyvinyl Alcohol/Polyurethane Nanofibers for Controlled Release of Doxurubicin and Its Anticancer Property. Fibers Polym 21, 1634–1642 (2020)).
Stipniece et al teaches functionalization of poly(vinyl alcohol) by modifying it with succinic anhydride in DMF to introduce carboxyl groups for the attachment of drug molecules (abstract and pg 16: 2 Materials and methods). The PVA used had a molecular weight of about 25k Daltons (pg 16, sec 2.1, 2nd ¶). The resulting nanosized needles are expected to be dispersed in materials of 2-10 micrometers (pg 19, conclusion).
Stipniece et al does not teach the inclusion of two or more biological actives with one being an aminothiol.
Qavamnia et al teaches it was known to incorporate doxorubicin-hydroxyapatite (an aminothiol active and a second active) into nano sized particles comprising PVA for treatment of cancers, such as bone cancer (abstract). Doxorubicin is taught as an alternative anticancer drug for various cancers, including breast (pg 1634, right column, about lines 21-23).
It would have been obvious to one of ordinary skill in the art to modify the delivery system of Stipniece et al by attaching a drug molecule as suggested via the carboxyl group, such as DOX as taught by the secondary reference as a known active for mucoadhesive delivery. When the active bonds, given the same active instantly claimed is disclosed in the prior art, and the PVA is modified with succinic acid as instantly claimed in the prior art, the bonding linkages would be expected to be the same as instantly claimed.
While the prior art does not appear to disclose the specific succinated amount, it would have been obvious to vary the amount based on the loading of the PVA, given the carboxyl groups provide the attachment site for the drug molecules.
Finally, while the prior art does not teach the crosslinking ester groups between the carboxyl and hydroxyl groups of the partially succinated polyvinyl alcohol, where the polymer prodrug produced has the same components instantly claimed and has the same reactive groups, it is reasonably expected that cross linking will inherently occur as part of the reaction process, given the same reactive groups are present in both the prior art and instant process. As such, the process would vary based on drug loading and particle size, thus varying the cross-linking amount and making instant claim 12 obvoius.
Allowable Subject Matter
Claims 15-17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims. Examiner notes the prior art does not disclose the coupling agents and catalysts specifically claimed as part of the process.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN J PACKARD whose telephone number is (571)270-3440. The examiner can normally be reached Mon 2-6pm and Tues-Fri (9am-6pm + mid-day flex).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN J PACKARD/ Primary Examiner, Art Unit 1612
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