DETAILED ACTION
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 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.
Status of the Claims
The response filed 01/20/2026 is acknowledged.
Claims 1-17 and 19-26 are pending.
Applicant’s election of Group I, claims 1-8, in the reply filed on 07/29/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 9-17 and 19-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/29/2025.
Claims 1-8 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Response to Arguments
Applicant's arguments filed 01/20/2026 have been fully considered but they are not persuasive.
Applicant has argued Codina, e.g., 0026, recommends to use a crystalline paclitaxel with a small crystal size, e.g., in the nanometer range, as this minimizes the risk of loss. Applicant argues Codina teaches away from the claimed invention since the claimed invasion requires that the taxane in the form of microcrystals wherein at least 90% of the at least one taxane is in the form of microcrystals having a crystal size of 10 µm.
This argument is unpersuasive.
Since Codina is silent to at least 90% of the taxane is in the form of microcrystals having a crystal size of 10 µm, it is not clear how the skilled artisan would conclude Codina teaches away from the claim limitation. There is nothing in Codina which specifically disparages particle sizes of 10 µm, e.g., examples showing sizes in the claimed range resulted in such low adhesion that no crystals were present after navigating to a target tissue site. Codina actually teaches the particles should be small, and offers a preference for crystal sizes in the range of nanometers. However, preferred embodiments do not constitute a teaching away from Codina’s broader teaching of small particle sizes. See MPEP 2123, II.
Further, the same paragraph in Codina goes on to explain the benefits of crystalline taxanes, including the fact that the crystalline forms offer high transfer to tissue, excellent drug retention in tissue, a means to achieve an extended effect, and offers high biological effectiveness with less probable restenosis (Codina, e.g., 0026). Thus, Codina suggests there are benefits to be derived from crystalline taxanes in a coating on a medical device which is applied in combination with a triacylglycerol within the scope of the claimed invention, e.g., trioctanoylglycerol, aka, tricaprylin (Codina, e.g., 0053).
Moreover, Codina is not the only reference cited in the rejection. Kangas teaches suspensions containing crystalline particle sizes, e.g., having a maximum particle size of about 10 µm or less (Kangas, e.g., 0011) for coating similar devices, e.g., balloon catheter (Kangas, e.g., 0068). Like Codina, Kangas teaches paclitaxel coated balloons having crystalline forms facilitate longer tissue residence times (Kangas, e.g., 0028). Since Kangas expressly teaches applying a crystalline drug having a particle size of about 10 µm or less to the outer surface of a device (Kangas, e.g., 0011), wherein the crystalline drug is a taxane and wherein the device is a balloon (Kangas, e.g., 0028), any fears the skilled artisan, reading Codina, may have harbored about drug particle sizes larger than nanometer size are explicitly resolved by the teachings of Kangas.
Applicant argues the method according to Kangas produces may smaller crystal sizes, i.e., crystals with a crystal size of mainly less than 10 µm, so that, according to the disclosure of Kangas, it is not possible to provide the advantageous crystal size distribution according to amended claim 1. Applicant agrees Kagans teaches applying microcrystals with a particle size of 10 µm or less. However, Applicant argues Kangas specially describes the production of everolimus seed crystals (Kangas, Example 1), and paragraph [0081] of Kangas discloses a crystal size of approximately 1 µm. Applicant additionally argues Kangas, Figs. 2, 6, 7, 9, and 10 show that the crystal size of the crystal coatings obtained according to Kangas, in which a seed crystal layer and an amorphous active ingredient layer are first applied to the surface of the medical device and then vapor annealing is carried out, is mainly in the range of less than 10 µm. Applicant argues the technical solution proposed in Kangas is not suitable for providing stably adhering crystal coatings of crystals, 90% of which have a crystal size of more than 10 µm.
These arguments are unpersuasive.
Based on Applicant’s remarks, it appears there is agreement that Kangas teaches applying microcrystals with a particle size of 10 µm or less. This teaching would have led the skilled artisan to modify Codina’s compositions comprising paclitaxel and trioctanoylglycerol (Codina, e.g., 0053) for coating a device with small crystals of paclitaxel on the surface (Codina, e.g., 0026), by preparing a suspension of paclitaxel microcrystals having a particle size of 10 µm or less and trioctanoylglycerol. Further, Kangas suggests particle size may vary and the size of the particle is a result effective parameter the skilled artisan would have optimized to retain the particles on the device surface (Kangas, e.g., 0070 too large size makes it easy to dislodge).
The claimed particle size range of wherein at least 90% of the at least one taxane is in the form of microcrystals having a crystal size of 10 µm is clearly within and overlapping with the range of 10 µm or less suggested by Kangas. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
To the extent that Applicant is arguing Kangas is not enabled to prepare a suspension having particle sizes of paclitaxel in the claimed range, it is noted that the claimed range is explicitly within and overlapping with a particle size of 10 µm or less suggested by Kangas (Kangas, e.g., 0011), and Kangas clearly teaches known techniques for optimizing particle sizes over the range of from about 20 µm to about 10 nm as desired (Kangas, 0055-0058).
Additionally, it is noted that Kangas, e.g., Fig. 2, teaches devices comprising a surface having a drug particle size, e.g., length, within which the claimed range resides. See Kangas, e.g., 0032, teaching crystals having a length of about 5-10 µm on the device.
Applicant has argued that it has unexpectedly been shown that the chemical, physical and biological properties of the tri-O-acyl glycerols, which are fully esterified with the medium-length fatty acids caprylic acid (octanoic acid), capric acid (decanoic acid), pelargonic acid (nonanoic acid) or undecanoic acid, are essential to enable a uniform and sufficiently adherent coating of medical devices with microcrystalline limus active agents "wherein at least 90% of the at least one limus active agent is present in the form of microcrystals with a crystal size of at least 10 µm.
This argument is unpersuasive.
Codina teaches excipients having formula 1 (Codina, e.g., claim 1) such as trioctanoylglycerol, aka, tricaprylin (Codina, e.g., 0053) offer uniform coatings of crystalline paclitaxel on devices (Codina, e.g., 0027) with excellent adhesion such that losses during navigation are very low (Codina, e.g., 0042). Thus, the proffered results appear to be expected from the teachings of the cited prior art. Expected beneficial results are evidence of obviousness. See MPEP 716.02(c), II.
Rejections Addressing Applicant’s Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4-5 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 4-5 depend from claim 1. Claim 1 has been amended to recites wherein at least 90% of the at least one taxane is in the form of microcrystals having a crystal size of 10 µm.
Claim 4 allows crystals having a size ranging from 1-300 µm.
Claim 5 allows at least 70% of the at least one taxane is in the form of microcrystals having a crystal size ranging from 10 µm to 100 µm.
Thus, claims 4 and 5 do not include all the limitations of claim 1 from which they depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 of this title, 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.
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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Codina, WO 2016015874 A1 and Kangas, US 20150250772 (cited previously).
Codina teaches a composition for coating a medical device comprising paclitaxel and a lipophilic excipient, e.g., caprylic acid triglyceride, i.e., trioctanoylglycerol (Codina, e.g., claim 6). Codina teaches the composition further comprising a solvent (Codina, e.g., claim 15). Codina teaches the form of the taxane may be crystalline and the form of the taxane may be controlled by selection of the solvent used in the preparation of the formulation for coating (Codina, e.g., 0024). Crystalline form of the taxane is desired for sustained dosing and longer effect to achieve better therapeutic results with less probable restenosis (Codina, e.g., 0026). Codina teaches the taxane having a small crystal size, e.g., in the range of nanometers (Codina, e.g., 0026).
Codina does not expressly teach a composition for coating the medical device containing a solvent in which the crystals of the taxane do not dissolve. Thus, Codina does not expressly teach the composition in the form of a suspension.
However, Kangas teaches microparticulate crystalline drug may be applied to medical devices as a coating when the coating formulation contains microcrystalline drug in a suspension (Kangas, e.g., 0052). Selecting excipients in which the drug is substantially undissolved enables the drug to be applied while remaining in the crystalline form (Kangas, e.g., 0043). Applying the drug in microcrystalline form in a suspension may be done to form coatings on the device with drug in crystalline form (Kangas, e.g., 0050-0055).
Like Codina, Kangas teaches coatings on medical devices containing paclitaxel in crystalline form facilitates longer tissue drug residence times (Kangas, e.g., 0028).
Kangas teaches non-polymeric excipients, such as oils (triglycerides) may be included in the coating to facilitate adhesion of the drug to the device (Kangas, e.g., 0040-0043). This teaching is congruent with Codina teaching the lipophilic excipient, e.g., caprylic acid triglyceride, i.e., trioctanoylglycerol (Codina, e.g., claim 6) is effective to retain crystalline paclitaxel on the device while also promoting paclitaxel transfer to tissue at the treatment site (Codina, e.g., 0030-0035).
Kangas clearly teaches the coating formulation may be in the form of a microcrystalline drug suspension (Kangas, e.g., 0052) which contains a vehicle in which the microcrystalline drug does not dissolve (Kangas, e.g., 0056: non-solvent for the drug such as water or heptane). Crystallization inducing solvents are listed in Kangas, e.g., 0065. Kangas exemplifies the choice of coating formulation non-solvent may be the same non-solvent used during crystallization and crystal sizing through grinding (Kangas, e.g., 0081-0083).
Kangas teaches applying drugs to the stent using a formulation in which the drug is dissolved may be undesirable because it results in uncontrolled crystal morphology, poor control over drug crystal location on the surface of the device, and poor adherence to the device surface (Kangas, e.g., 0070).
Thus, Kangas provides motivation for the skilled artisan to have modified coating formulations containing paclitaxel and a lipophilic excipient, e.g., caprylic acid triglyceride, i.e., trioctanoylglycerol as known from Codina by using a non-solvent for paclitaxel for a number of benefits including increased control over crystalline paclitaxel form and particle size, improved control over the location of crystalline drug on the device surface, and improved adherence of the crystalline drug particles to the device surface.
Kangas teaches applying microcrystals with a particle size of 10 µm or less. This teaching would have led the skilled artisan to modify Codina’s compositions comprising paclitaxel and trioctanoylglycerol (Codina, e.g., 0053) for coating a device with small crystals of paclitaxel on the surface (Codina, e.g., 0026), by preparing a suspension of paclitaxel microcrystals having a particle size of 10 µm or less and trioctanoylglycerol. Further, Kangas suggests particle size may vary and the size of the particle is a result effective parameter the skilled artisan would have optimized to retain the particles on the device surface and obtain a uniform coating (Kangas, e.g., 0070 too large size makes it easy to dislodge).
The claimed particle size range of wherein at least 90% of the at least one taxane is in the form of microcrystals having a crystal size of 10 µm is clearly within and overlapping with the range of 10 µm or less suggested by Kangas. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious before the effective filing date of the presently claimed invention to modify compositions comprising a taxane and caprylic acid triglyceride by formulating the coating as a suspension containing a solvent system in which the drug does not dissolve and having a crystal size of 10 µm or less so that the drug remains in desired crystalline form as suggested by Kangas with a reasonable expectation of success. The skilled artisan would have seen this modification as the use of known solvent selection techniques to improve Codina’s coating compositions in the same way. The skilled artisan would have been motivated to formulate Codina’s taxane coating compositions in the form of a suspension using a solvent in which taxane microcrystals having a crystal size of 10 µm or less do not dissolve as suggested by Kangas to produce a coating containing crystalline forms of taxane thereby achieving the sustained dosing and longer taxane effect to achieve better therapeutic results with less probable restenosis desired by Codina while also enjoying a number of benefits including increased control over crystalline paclitaxel form and particle size, improved control over the location of crystalline drug on the device surface, and improved adherence of the crystalline drug particles to the device surface.
. The skilled artisan would have had a reasonable expectation of success because Kanga expressly teaches suspensions of microcrystalline drug may be formulated with non-solvents for the drug to enable drug coatings containing crystalline drug forms having improved properties.
Applicable to claim 2: Codina teaches paclitaxel (Codina, entire document, e.g., 0053 and claims).
Applicable to claim 3: Codina teaches a coating formulation having mass ratio of 20 tricaprylin to 80 paclitaxel (Codina, e.g., 0053). This is an example in the claimed ranges.
Applicable to claims 4-5: Kangas teaches micron sized drug crystals (Kangas, e.g., 0051-0052), e.g., having a size in the claimed ranges, e.g., preferably having a mean particle size of less than 20 microns, e.g., less than about 10 microns (Kangas, e.g., 0053-0055). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. Further particle size may vary and the size of the particle is a result effective parameter the skilled artisan would have optimized to retain the particles on the device surface (Kangas, e.g., 0070 too large size makes it easy to dislodge).
Applicable to claim 6: Kangas teaches wherein the drug has a crystallinity in the claimed range, e.g., about 100% (Kangas, e.g., 0073 and 0077). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
Applicable to claim 7: Kangas clearly names heptane as a non-solvent for so that the drug is substantially undissolved (Kangas, e.g., 0056-0057). Heptane has properties consistent with those claimed as evidenced by the specification, e.g., pp. 44-45 table 2. This clear teaching in Kangas would have prompted the skilled artisan to use heptane as a non-solvent vehicle to modify coating formulations suggested by Codina as a suspension for the benefits reported in Kangas.
As evidenced by the specification, trioctanoylglycerol is soluble in heptane (Spec, e.g., pg. 42:15-19).
Claim 8 is included in this rejection as further limiting an optional solvent mixture limitation of claim 1.
Accordingly, the subject matter of claims 1-8 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Codina, WO 2016015874 A1 and Kangas, US 20150250772 (cited previously) as applied to claims 1-8 above, and further in view of Bui-Khac, US 5759539.
The combined teachings of Codina and Kangas teach a suspension according to claim 1 as enumerated above. The combined teachings of Codina and Kangas do not expressly teach the paclitaxel suspension having a solvent mixture of at least one polar organic solvent and at least one nonpolar organic solvent as set forth in claim 8. To the extent that claim 8 is limiting, solvent mixtures having the characteristics set forth in claim 8 were known and used to induce crystallization of paclitaxel and were known for maintaining desired crystalline nature of paclitaxel in suspension as evidenced by the teachings of Bui-Khac.
For example, Bui-Khac teaches the solvent mixture of ethyl acetate and hexane was known to induce crystallization of paclitaxel and allow manipulation of the crystalline suspension, e.g., filtration (Bui-Khac, e.g., c8:5-32).
Kangas teaches vehicle which may be effective to induce crystallization of the drug includes similar mixed solvents such as heptane/ethyl acetate (Kangas, e.g., 0065).
It would have been obvious before the effective filing date of the presently claimed invention to modify compositions for coating comprising a taxane and caprylic acid triglyceride by formulating the coating composition as a suspension containing a solvent system in which the taxane does not dissolve so that the drug remains in desired crystalline form as suggested by Kangas with a reasonable expectation of success. The skilled artisan would have seen this modification as the use of known solvent selection techniques to improve Codina’s coating compositions in the same way. The skilled artisan would have been motivated to formulate Codina’s taxane coating compositions in the form of a suspension using a solvent in which taxane microcrystals do not dissolve as suggested by Kangas to produce a coating containing crystalline forms of taxane thereby achieving the sustained dosing and longer taxane effect to achieve better therapeutic results with less probable restenosis desired by Codina while also enjoying a number of benefits including increased control over crystalline paclitaxel form and particle size, improved control over the location of crystalline drug on the device surface, and improved adherence of the crystalline drug particles to the device surface. The skilled artisan would have been motivated to formulate the taxane microcrystal coating suspension suggested by the combined teachings of Codina and Kangas using known solvent systems effective to induce and maintain crystallization of paclitaxel such as ethyl acetate and hexane as reported by Bui-Khac to maintain the paclitaxel crystalline form and particle size as recommended by Kangas. The skilled artisan would have had a reasonable expectation of success because Kangas suggests similar solvents and solvent mixtures, e.g., heptane and ethyl acetate as effective to suspend the drug.
Accordingly, the subject matter of claims 1-8 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent 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 WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A WAX can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
/SUSAN T TRAN/Primary Examiner, Art Unit 1615