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 .
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.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13 in the reply filed on 27 February 2026 is acknowledged.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 27 February 2026.
Claim Interpretation
Claim 1 recites a method of coating a medical device. As such, it is understood that the starting material of the method is an uncoated medical device and the product is a coated medical device. As such, the phrase “contacting the medical device” on the second to last line of claim 1 is understood to have appropriate antecedent basis because the method of claim 1 is understood to begin with an uncoated medical device.
As to claim 10, it would appear that the additional step recited by the claim must occur prior to the step of suspending therapeutic agent crystals in a first solution.
Claim Rejections - 35 USC § 102(a)(1) – Anticipation
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(s) 1-3 and 7-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zeng et al. (US 2020/0038559 A1).
Zeng et al. (hereafter referred to as Zeng) is drawn to an elutable coating on a substrate, as of Zeng, title and abstract. Zeng teaches the following, as of paragraph 0078, reproduced below.
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As to step (a) of claim 1, Zeng teaches mixing crystalline everolimus with excipients such as ethylcellulose and poly(lactic-co-glycolic) acid (i.e. PLGA), as of the above-reproduced paragraph from Zeng. While Zeng does not explicitly teach that this would have resulted in encapsulated everolimus crystals, the skilled artisan would have expected that the method of Zeng would have resulted in encapsulated everolimus crystals even if this feature was not recognized by Zeng. Something which is old (e.g. the method of Zeng) does not become patentable upon the discovery of a new property (that the everolimus crystals become encapsulated), and this feature need not have been recognized at the time of filing. See MPEP 2112 (I & II).
As to step (b) of claim 1, Zeng teaches contacting the dispersed everolimus crystals and excipients with a balloon, which in the context of Zeng is a medical device, to coat said balloon.
As to claim 1, the examiner notes that once a reference teaching a product (or in this case process) appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. See MPEP 2112(V). In this case, Zeng appears to be substantially identical except for being silent as to whether the method of Zeng would have resulted in encapsulated everolimus crystals prior to coating. However, the instant specification appears to indicate that mixing everolimus crystals with excipients results in encapsulation; see the instants specification at least on page 13, paragraph 0083. This is understood to be sufficient to shift the burden to applicant in accordance with MPEP 2112(V). The examiner clarifies that citation to the specification is not impermissible hindsight reasoning because the examiner is citing to the specification to provide the reasoning necessary to shift the burden in accordance with the guidelines of MPEP 2112(V).
As to claim 2, the everolimus of Zeng reads on the additional requirements of this claim.
As to claim 3, Zeng teaches ethylcellulose, as of paragraph 0078, reproduced above.
As to claim 7, Zeng teaches an inflatable balloon as of paragraph 0053.
As to claim 8, Zeng teaches an expandable stent as of paragraph 0075.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1-3, 5, and 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US 2020/0038559 A1).
Zeng et al. (hereafter referred to as Zeng) is drawn to an elutable coating on a substrate, as of Zeng, title and abstract. Zeng teaches the following, as of paragraph 0078, reproduced in the anticipation rejection above.
As to step (a) of claim 1, Zeng teaches mixing crystalline everolimus with excipients such as ethylcellulose and poly(lactic-co-glycolic) acid (i.e. PLGA), as of the above-reproduced paragraph from Zeng. While Zeng does not explicitly teach that this would have resulted in encapsulated everolimus crystals, the skilled artisan would have expected that the method of Zeng would have resulted in encapsulated everolimus crystals even if this feature was not recognized by Zeng. Something which is old (e.g. the method of Zeng) does not become patentable upon the discovery of a new property (that the everolimus crystals become encapsulated), and this feature need not have been recognized at the time of filing. See MPEP 2112 (I & II).
As to step (b) of claim 1, Zeng teaches contacting the dispersed everolimus crystals and excipients with a balloon, which in the context of Zeng is a medical device, to coat said balloon.
As to claim 1, purely en arguendo and for the purposes of this ground of rejection, the examiner takes the position that Zeng teaches all of the claimed requirements but not in the same embodiment. As such, for the purposes of this ground of rejection, the examiner understands that while the prior art teaches all of the claimed components, the prior art is not anticipatory insofar as these components must be selected from various lists/locations in the prior art reference. It would have been prima facie obvious; however, to have selected the recited components from various lists/locations in the prior art reference and to have combined them together. This is because such a modification would have represented nothing more than the predictable use of prior art components according to their established functions. Combining separate prior art components (from a single prior art reference) according to known methods to yield predictable results is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 1, the examiner notes that once a reference teaching a product (or in this case process) appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. See MPEP 2112(V). In this case, Zeng appears to be substantially identical except for being silent as to whether the method of Zeng would have resulted in encapsulated everolimus crystals prior to coating. However, the instant specification appears to indicate that mixing everolimus crystals with excipients results in encapsulation; see the instants specification at least on page 13, paragraph 0083. This is understood to be sufficient to shift the burden to applicant in accordance with MPEP 2112(V). The examiner clarifies that citation to the specification is not impermissible hindsight reasoning because the examiner is citing to the specification to provide the reasoning necessary to shift the burden in accordance with the guidelines of MPEP 2112(V). The examiner also notes that according to MPEP 2112(V), first paragraph, whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same. As such, the examiner takes the position that shifting the burden to applicant in view of MPEP 2112(V) is appropriate in an obviousness rejection.
As to claim 2, the everolimus of Zeng reads on the additional requirements of this claim.
As to claim 3, Zeng teaches ethylcellulose, as of paragraph 0078, reproduced above.
As to claim 5, Zeng teaches application to the medical device by spraying, as of a list as of paragraph 0068.
As to claim 7, Zeng teaches an inflatable balloon as of paragraph 0053.
As to claim 8, Zeng teaches an expandable stent as of paragraph 0075.
Allowable Subject Matter
Claims 4 and 6 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 9-13 are allowed.
The examiner has presented the following rationale for not rejecting claims 4, 6, and 9-13 over prior art.
As relevant prior art, the examiner cites Zeng et al. (US 2020/0038559 A1), which was cited in the rejection above. Zeng et al. (hereafter referred to as Zeng) is drawn to an elutable coating on a substrate, as of Zeng, title and abstract. Zeng teaches mixing crystalline everolimus with excipients such as ethylcellulose and poly(lactic-co-glycolic) acid (i.e. PLGA), as of paragraph 0078. Zeng then teaches contacting the everoliums, ethylcellulose, and PLGA with a balloon, wherein the balloon is a medical device, as of Zeng, paragraph 0078.
Zeng does not teach acetyl tri-butyl citrate, (which is abbreviated as ATBC in the instant claims). It would not have been obvious for the skilled artisan to have added ATBC in the required amount for at least the following reasons.
As an initial matter, the examiner notes that acetyl tributyl citrate (ATBC) was known in the art as a plasticizer prior to the effective filing date. In support of this position, the examiner cites Liu (US 2005/0182156 A1), which indicates that ATBC is a plasticizer as of the title and as of at least paragraph 0002.
The examiner notes here that Zeng does not teach a plasticizer. As such, it appears that there may have been no motivation for the skilled artisan to have added ATBC to the method of Zeng. This is because ATBC would have been known as a plasticizer at the time of filing, and Zeng does not appear to provide motivation for the skilled artisan to have further included a plasticizer.
As relevant prior art, the examiner cites Snejdrova et al. (Eva Snejdrova and Milan Dittrich (2012). Pharmaceutical Applications of Plasticized Polymers, Recent Advances in Plasticizers, Dr. Mohammad Luqman (Ed.), ISBN: 978-953-51-0363-9, InTech, Available from: http://www.intechopen.com/books/recent-advances-in-plasticizers/pharmaceutical-applications-of-plasticizedpolymers pages 69-90 and two additional pages). Snejdrova et al. (hereafter referred to as Snejdrova) is drawn to the application of plasticizers in pharmaceuticals. Snejdrova provides teachings regarding plasticized polymers as coatings, as of Snejdrova, page 69. However, the teachings of Snejderova appear to be drawn to plasticizers for oral administration, as of Snejdrova, page 69, first paragraph in item #2. This appears to differ from both Zeng and the instant invention, as both Zeng and the instant invention are drawn to a method of making an implantable medical device rather than a method of making an oral pharmaceutical preparation.
Snejdrova teaches which plasticizers are most likely to be used with which polymers as of the table on pages 83-84. In this table, Snejdrova suggests using dibutyl sebacate to plasticize ethyl cellulose on page 83. Snejdrova suggests a wide range of plasticizers to plasticize poly(lactide-co-glycolide) on page 84. While Snejdrova suggests “oligoesters” genetically, Snejdrova does not specifically point out acetyl tributyl citrate. Elsewhere in the reference, Snejdrova teaches acetyl tributyl citrate; however, it is to plasticize proteins, as of Snejdrova, page 73, bottom paragraph and page 84, top entry in table. Snejdrova also teaches tributyl citrate (albeit not acetyl tributyl citrate) as the best plasticizer for Eudragit, as of Snejdrova, page 72. As such, while Snejdrova teaches acetyl tributyl citrate as a plasticizer and both ethylcellulose and PLGA as polymers to be plasticized, Snejdrova does not teach that acetyl tributyl citrate is the optimum plasticizer for either ethylcellulose or PLGA.
As additional relevant prior art, the examiner cites Zeng et al. (US 2021/0300938 A1). Zeng et al. (hereafter referred to as Pascal after the second named inventor) is drawn to methods for crystallization of drugs, as of Pascal, title and abstract. Pascal teaches crystallization of everolimus on a stent and teaches acetyl tributyl citrate, as of Pascal, paragraph 0047, which is reproduced below.
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In the above-reproduced paragraph, Pascal teaches crystallizing everolimus in combination with acetyl tri-butyl citrate (ATBC). However, there is no evidence that the ATBC encapsulates the everolimus crystals. Nevertheless, even if it were assumed, purely en arguendo that the ATBC of Pascal encapsulates everolimus crystals, Pascal is deficient with respect to claims 4, 6, and 9-13 because Pascal does not teach ethyl cellulose.
The instant specification provides the following comparative testing as of the table bridging pages 21-22.
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Sample 3 appears to have resulted in significantly slower drug release as compared with samples #1 and #2, as of the instant specification on page 21 paragraph 0106 as well as figure 8 of the instant application, which is reproduced below with annotation by the examiner to explain which line in the figure corresponds with which sample.
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In order to overcome a case of prima facie obviousness based upon unexpected results, the claimed invention must be compared with the closest subject matter to actually exist in the prior art. See MPEP 716.02(e). As best understood by the examiner, the method of making sample 2, which comprises ethylcellulose but lacks acetyl tributyl citrate, appears to be as close to the claimed invention of claims 4, 6, and 9-13 as the method of Zeng. Additionally, the method of making sample 1, which comprises acetyl tributyl citrate but lacks ethylcellulose, appears to be as close to the claimed invention of claims 4, 6, and 9-13 as the method of Pascal. The examiner notes that MPEP 716.02(e)(II) states that showing unexpected results over one of two equally close prior art references will not rebut prima facie obviousness. However, in this case, it appears that applicant has compared the claimed invention to both the method of Zeng (in Sample 2) and the method of Pascal (in Sample 1); as such, applicant has met the burden of showing comparative testing over two of two close prior art references.
In order to overcome a case of prima facie obviousness, the results must be unexpected, and of statistical and practical significance. See MPEP 716.02(b)(I). In this case, the slower release appears to be of statistical significance. It is also of practical significance because a slower drug release allows the therapeutic effect of the drug to be present for a longer period of time, which has a practical effect. Additionally, the examiner takes the following position to explain why this result would have been unexpected.
The examiner reviewed Snejdrova in order to best determine what the skilled artisan would have expected regarding the relationship of using a plasticizer to the rate of drug release. The teachings of Snejdrova appear to indicate that the inclusion of a plasticizer either does not change the release rate or increases the release rate of active agent, or decreases the release rate of active agent. See Snejdrova, page 78, second paragraph in item #7, reproduced below with annotation by the examiner.
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As such, based upon the teachings of the above-reproduced paragraph, it appears that the effect of a plasticizer on drug release would have been unpredictable.
In a similar vein, the examiner cites Shen et al. (US 2009/0324716 A1), paragraph 0002, relevant text reproduced below.
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The examiner understands the phrase “compromise the modified release properties of the polymer” to indicate that the plasticizer results in faster drug release.
As such, the prior art appears to teach either that the skilled artisan would have expected that the inclusion of a plasticizer would have either resulted in faster drug release or the effect of the plasticizer on drug release would have been unpredictable. In contrast, applicant used acetyl tributyl citrate as a plasticizer with ethylcellulose and achieved slower drug release. This slower drug release would appear to have been an unexpected result in view of the teachings of Snejdrova and Shen. As such, in view of this, the examiner has decided not to reject claims 4, 6, and 9-13 as obvious.
As additional relevant prior art, the examiner cites Kangas (US 2016/0331564 A1). Kangas is drawn to a medical device such as balloon catheter which comprises everolimus, as of Kangas, title and abstract. The composition and method of making the composition of Kangas comprises acetyl tributyl citrate (abbreviated as ATBC), as of Kangas, paragraphs 0107-0108, but appears to lack ethylcellulose and also appears to lack PLGA. Kangas teaches the effect of ATBC on drug release in paragraph 0107, in which Kangas states that ATBC may help release the drug from the balloon. The examiner understands this as a teaching that the skilled artisan would have expected ATBC to have speeded drug release. In contrast, in the claimed method invention, ATBC appears to result in slower release of the drug. This appears to be contrary to what the skilled artisan would have expected based upon the teachings of Kangas. Proceeding contrary to the accepted wisdom is evidence of non-obviousness. See MPEP 2145(X)(D)(3). In this case, the accepted wisdom based upon the teachings of Kangas is that ATBC would speed up drug release. In contrast to that accepted wisdom, applicant appears to have found that ATBC slows drug release rather than speeds up drug release.
Conclusion
Less than all claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
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