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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/30/2026 has been considered by the examiner.
Status of the Claims
The response filed 06/30/2026 is acknowledged.
Claims 1-2, 4-6, 8-17, 19-21, and 23-26 are pending.
Claims 9-17, 19-21, and 23-26 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/23/2025.
Claims 1-2, 4-6, and 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.
Response to Arguments
Applicant's arguments filed 06/30/2026 have been fully considered but they are not persuasive.
Applicant argues Kangas teaches away from the amended claims as provided herewith, in particular wherein at least 90% of the at least one limus agent is in the form of microcrystals having a crystal size of at least 10 µm. Applicant argues in paragraph [0011] of Kangas, the maximum particle size of the crystalline form of the drug in Kangas' seed layer is about 10 µm or less. Applicant argues in paragraph [0055] of Kangas, the microparticulate drug crystals have a mean particle size of less than 10 µm. Applicant argues the examples of Kangas use seed crystals that are -1 µm ("Average particle size is about 1 pm"). See Example 1 of paragraph [0081]. Applicant argues the SEM images and examples of Kangas show that the crystals are less than 10 µm. Applicant argues one skilled in the art reading Kangas as a whole, including paragraphs [0011] and [0055] and the examples, understands that crystal sizes of the drug of less than 10 µm are highly preferred and are what was prepared.
This argument is unpersuasive.
Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. Kangas clearly teaches the seed nucleating microcrystals my range up to about 20 µm (Kangas, e.g., 0053). The skilled artisan would have understood Kangas, e.g., ¶ 0053, as teaching a broader range of nucleating particle sizes which may be present in a suspension for coating the device surface with a seed microcrystalline layer.
Applicant argues one skilled in the art reading Kangas as a whole understands that only a very minor fraction of the drug is in crystalline form. Applicant argues in paragraph [0051] of Kangas, the coating on a device is accomplished by applying an amorphous drug coating to a device that has been first nucleated with microparticle crystalline drug (a seed layer) to induce crystallization during the annealing step. Applicant argues that Example 1 and paragraphs [0083]-[0084] of Kangas describes the amount of microparticle crystalline drug in the seed layer as "[a] very small amount" and the weight of the seed layer as being "too little to quantify gravimetrically (a rough estimate of 1-3 pg)," while the subsequently applied layer with the amorphous drug is "100-200 pg."
These arguments are unpersuasive.
As stated in the remarks, ¶s [0083]-[0084] of Kangas refer to the coating on the device rather than the suspension for coating the medical device as claimed. Therefore it is not clear how ¶s [0083]-[0084] of Kangas are relevant to the suspension used to coat the device. It is acknowledged that this example uses a suspension with particles sized 1 µm. However, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. Kangas clearly teaches the seed nucleating microcrystals my range up to about 20 µm (Kangas, e.g., 0053). The skilled artisan would have understood Kangas, e.g., ¶ 0053, as teaching a broader range of nucleating particle sizes which may be present in a suspension for coating the device surface with a seed microcrystalline layer.
Applicant argues that Kangas explicitly states, "Either way it was considered that that nucleation with microcrystalline drug particles should not provide a reliable crystalline coating for a medical device." Applicant concludes one skilled in the art reading Kangas as a whole understands that the amount of microparticle crystalline drug present is de minimis, and significantly less than at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of at least 10 µm.
This argument is unpersuasive.
It appears Applicant is referring to Kangas, ¶ 0059. Applicant appears to be implying that Kangas teaches the suspension is not useful for providing a crystalline coating on a medical device. However, consideration of the full paragraph and the teachings of Kangas as a whole reveals the full context and the skilled artisan would have understood this quoted section differently. It is unclear how the amount of crystalline drug present in the coating on the device in Kangas example 1 is relevant to the percent of microcrystals having a size of at least 10 µm present in the suspension.
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Here, the quoted section refers to the state of the art before their disclosure, i.e., it was considered that that nucleation with microcrystalline drug particles should not provide a reliable crystalline coating for a medical device [before] we surprisingly discovered that microcrystalline drug [applied from a suspension] can be used as a nucleating agent. Kangas, ¶s [0083]-[0084] and indeed example 1, simply teach that only a very small amount of microcrystals [rather than a thick microcrystalline layer] are required on the device surface to effectively provide a reliable crystalline coating on the medical device.
Applicant argues Codina also teaches away from the claims as provided herein and does not remedy this deficiency of Kangas. Applicant argues Codina explicitly states that "it is recommended to use crystalline paclitaxel with a small crystal size because this can minimize the risk of losses. Preferably the crystal size is [in] the range of nanometers." (Emphasis added) See lines 30-32 on page 8 of Codina. Applicant argues one skilled in the art reading Codina understands that markedly smaller crystal sizes (nanometers) are superior to larger crystal sizes of 1 µm and 10 µm as recited in the amended claims of the present application.
This argument is unpersuasive.
There is nothing in Codina which specifically disparages particle sizes of 1 µm or greater or 10 µm or greater, 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, Kangas clearly teaches the seed nucleating microcrystals my range up to about 20 µm (Kangas, e.g., 0053). The skilled artisan would have understood Kangas, e.g., ¶ 0053, as teaching a broader range of nucleating particle sizes which may be present in a suspension for coating the device surface with a microcrystalline limus drug. Since Kangas expressly teaches applying a crystalline drug having a particle size of about 10 µm or less or about 20 µm or less to the outer surface of a device (Kangas, e.g., 0011 and 0053), wherein the crystalline drug is a limus drug (Kangas, e.g., 0036) 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.
The claimed particle size range of having a crystal size of at least 1 µm and wherein at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of 10 µm are clearly within and overlapping with the range of 10 µm or less or 20 µm or less suggested by Kangas. 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.
It is additionally noted that 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 drug 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).
Applicant argues Codina provides that the preferable amorphous/crystalline paclitaxel ratio in weight is 10/90 to 50/50 so that it achieves the synergistic effect of the immediate effect of amorphous paclitaxel and long-lasting effects of crystalline paclitaxel. See lines 17-28 on page 9 of Codina. Applicant argues that based on this disclosure of Codina, one skilled in the art is taught away from having a high concentration of crystalline drug, such as at "wherein the at least one tri-O-acylglycerol and the at least one limus active agent are present in a mass ratio of 10% - 30% tri-O-acylglycerol to 90% - 70% limus active agent", because the aforementioned synergistic effect would not be achieved due to the too high concentration of crystalline drug.
This argument is unpersuasive.
It is not clear what relevance the amorphous/crystalline ratio of the drug in Codina’s coating has to the percent of microcrystals having a size of at least 10 µm in the coating suspension, particularly since Kangas teaches crystalline drug is applied from a suspension distinct from the amorphous drug coating composition. The crystal size is not a measure of the amount of drug in the coating suspension which is crystalline.
With respect to the limitation of wherein the at least one tri-O-acylglycerol and the at least one limus active agent are present in a mass ratio of 10% - 30% tri-O-acylglycerol to 90% - 70% limus active agent, it is noted that Codina teaches a drug to trioctanoylglycerol, aka, tricaprylin ratio of 75/25 to 85/15, preferably 80/20 to balance coating integrity and losses during navigation with optimal drug concentration and transfer to the tissue to be treated. (Codina, e.g., 0023). 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.
Applicant has argued a prima facie case of obviousness can be rebutted by showing that a range is critical. See MPEP #2144.05(III)(A). Applicant argues that as provided by the present application, the size of the microcrystals of the at least one limus active agent is critical. Applicant argues the crystals of the limus active agent should have a size of at least 1 µm. Applicant argues that in preparing the suspension of the present invention, it has been found that stable suspensions can be obtained only when the at least one limus active agent has substantially no crystals with a crystal size of less than 1 µm. Applicant argues the specific recited tri-O-acylglycerols enabled the formation of stable suspensions of microcrystalline limus active agents (as demonstrated by the examples in the present application) with the microcrystalline limus active agent that has at least 1 µm and wherein at least 90% of the at least one limus active agent has microcrystalline limus active agent of at least 10 µm. Applicant has argued that as provided in the present application, a problem with crystalline limus active agents is that "suspensions of particles larger than 1 - 5 µm tend to sediment rapidly, which subsequently makes uniform coating with microcrystalline limus active agent from suspensions much more difficult." Lines 19-21 on page 3 of the present application. Applicant argues that unexpectedly, the claimed suspensions with the recited specific tri-O-acylglycerols and crystalline sizes of the at least one limus active agent ("at least one limus active agent in the form of microcrystals having a size of at least 1 µm " and "wherein at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of at least 10 µm " (Emphasis added)) exhibited no sedimentation of the microcrystals, even over extended periods (>100 hours), no dissolution of the microcrystals, uniform distribution of the microcrystals in the suspension ("floating" behavior), and preservation of original crystal morphology and size distribution. Applicant argues the experimental data in the examples of the present application clearly demonstrate that other tri-O-acylglycerols, such as those with shorter or longer chain lengths, failed to provide stable suspensions, and even minor structural variations resulted in either dissolution or sedimentation of the limus active agent microcrystals. Applicant argues that Table 9, Examples 2 and 3, triacetin (Example 2), trihexanoylglycerol (Example 2), triheptanoylglycerol (Example 3), tridodecanoylglycerol (Example 2) and tritetradecanoylglycerol (Example 2) resulted in dissolution and/or led to sedimentation and instability.
These arguments are unpersuasive.
The claimed invention does not require that the suspension contains no crystals with a size of less than 1 µm in the suspension. It is noted that that the suspension requires at least one limus active agent in the form of microcrystals having a crystal size of at least 1 µm. However, the claim does not exclude additional limus actives or additional particle populations having a size of less than 1 micron.
In response to Applicant’s argument that one skilled in the art understands from the present application, that if the crystal size is less than 1 µm, the limus active agent dissolves too quickly and the suspension is unstable: it is noted that while this may have been shown in the examples for suspensions containing two particular limus actives (rapamycin and everolimus), a narrow particle size range, e.g., sized in the range of 10-40 µm (Spec, e.g., ¶ spanning pp. 130-131 and example 3), specific amount of a particular tri-O-acylglycerol, and a specific volume of a particular solvent combination, i.e., 100 mL of solvent containing 1.56 mL ethyl acetate and 84.4 mL heptane (Spec, example 2, pg. 131:29-32 and example 3), the claims are not limited to these specific compositions containing particular amounts of specific limus actives and amounts, tri-O-acylglycerol amounts, more limited particle size ranges, and solvent combination and volume.
There is insufficient data to establish criticality over the full scope of suspension compositions reading on, e.g., any limus active in any amount, a broader particle size range including an unbound upper limit on particle size, and variable solvent systems encompassed by the invention as presently claimed. Regarding solvents, for example, since heptane is a non-solvent for limus actives (Kangas, e.g., 0056), the skilled artisan would expect less solubility of 1 µm sized crystals if the solvent system contains a different solvent system, e.g., more heptane, e.g., 100% heptane or a greater volume of heptane.
Objective evidence of unexpected results must be commensurate in scope with the claimed invention. See MPEP 716.02(d). As explained above, the proffered evidence in Examples 2 and 3 showing suspension stability over 100 hours has been shown for suspensions containing single limus actives (rapamycin and everolimus), a narrow particle size range, e.g., 100% of particles sized in the range of from 10-40 µm (Spec, e.g., ¶ spanning pp. 130-131 and example 3), specific amount of a particular tri-O-acylglycerol, and a specific volume of a particular solvent combination, i.e., 100 mL of solvent containing 1.56 mL ethyl acetate and 84.4 mL heptane (Spec, example 2, pg. 131:29-32 and example 3). The claimed invention reads on any limus active or combination thereof in any amount, trioctanoylglycerol, trinonanoylglycerol, tridecanoylglycerol, or triundecanoylglycerol in any amount, a broader particle size range including an unbound upper limit on particle size, and variable solvent systems which deviate significantly from the proffered evidence shown. The data does not support the size ranges encompassed by claim 1, or the ranges recited in claim 4 or 5 in combination with the limited requirements of claim 1.
Rejections Addressing Applicant’s Amendment
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 1-2, 4-6 and 8 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.
Claim 1 includes the limitation of at least one limus active agent in the form of microcrystals having a crystal size of at least 1 µm, and wherein at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of at least 10 µm.
It is not clear if the combination of limitations was intended to require two distinct microcrystal particle populations or if the combination of limitations was intended to require a single microcrystal particle population with two size requirements. In each case “the at least one limus active agent” would be interpreted to mean the limus active agent is the same.
In the former case the claim would require two separate microcrystal particle size populations of the same limus active agent and the particle size limitations define two distinct particle size limitations, i.e., one particle population at least 1 µm in size and the second particle population defined by at least 90% being a size of at least 10 µm.
In the latter case the claim would require a single microcrystal particle population of the same limus active agent and the microcrystal particle size limitations would refer to the same microcrystal particle population, e.g., a lower bound of 1 µm and at least 90% of the microcrystals having a size of at least 10 µm.
It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See 2173.02, II.
Dependent claims do not clarify this issue.
Claims 4 and 5 do not indicate which microcrystal size range of claim 1 is intended to be further limited and may refer to separate particle populations, e.g., claim 4 applies to the population having a size of at least 1µm, while claim 5 refers to the particle size population having a size of at least 10 µm.
Clarification is required.
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 1-2, 4-6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kangas, US 20150250772 and Codina, WO 2016015874 A1.
Kangas teaches suspension compositions comprising microparticulate crystalline limus drug, which suspension may be applied to medical devices as a coating, and wherein the coating formulation contains microcrystalline drug in a suspension (Kangas, e.g., 0051-0057, e.g.,0052 and claims 1-12). 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). The suspension enables seeding the surface of the medical device with desired microcrystalline morphology, which in turn improves drug crystal adherence to the device surface and optimal particle size to reduce risk of dislodging the drug from the surface (Kangas, e.g., 0070). This technique is particularly useful for optimizing drug release from the coating, e.g., ratio of microcrystalline to other drug polymorphs is useful for tailoring drug release from the coating (Kangas, e.g., 0072). Kangas teaches various limus drugs consistent with claim 2. See Kangas, e.g., 0035-0037 and claims 1-5. Microcrystalline everolimus suspensions are exemplified (Kangas, e.g., Example 1-4, 0079-0097). The suspensions are formulated for coating medical devices, e.g., stent (Kangas, e.g., 0096), and balloons, catheters, catheter ballons (Kangas, e.g., 0046-0048).
Regarding the limitation of microcrystals having a size of at least 1 µm and wherein at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of at least 10 µm: Kangas the coating composition comprising a crystalline form having a particle size of about 10 µm or less (Kangas, e.g., 0011) as a nucleating crystal size (Kangas, e.g., 0050-0053). However, Kangas also teaches the nucleating microcrystalline drug may have a size up to about 20 µm (Kangas, e.g., 0053, 0055, 0059, 0061 and 0064). Kangas teaches the size is preferably optimized so that a reasonably stable coating dispersion can be obtained (Kangas, e.g., 0058).
Kangas clearly teaches crystalline everolimus can be used to obtain polymer-independent sustained drug release coatings (Kangas, e.g., 0072 and 0096). Thus, while certain specific embodiments in Kangas demonstrate smaller crystals, e.g., 10-20 µm or less, the skilled artisan understood that, in order to pursue longer release duration, crystals larger than 10-20 µm or less may be used in the supsension. That is, from Kangas, the skilled artisan understood that the size of the crystals in the suspension were recognized as a result effective parameter the skilled artisan could optimize to balance the need for a reasonably stable suspension on one hand with a desired release duration on the other.
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, the skilled artisan understood from Kangas that the size of the particle in the suspension is a result effective parameter the skilled artisan would have optimized to balance suspension stability and the need to retain the particles on the device surface (Kangas, e.g., 0070 too large size makes it easy to dislodge) with the needs of sustained release (Kangas, e.g., 0072 and 0096).
The claimed range for crystal size - of at least 1 µm and wherein at least 90% of the at least one limus active agent is in the form of microcrystals having a crystal size of at least 10 µm - overlap with the range suggested by Kangas, e.g., about 10-20 µm or less.
Kangas teaches non-polymeric excipients, such as oils (triglycerides) may be included in the coating suspension to facilitate adhesion of the drug to the device (Kangas, e.g., 0040-0043).
Kangas does not expressly teach wherein the triglyceride is selected from the group consisting of trioctanoylglycerol, trinonanoylglycerol, tridecanoylglycerol, and triundecanoylglycerol as claimed.
However, triglycerides within the scope of the claimed invention were known and used for coating compositions containing similar drugs, which compositions are useful to coat the same devices reported by Kangas, e.g., stents, catheters, etc.
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 drug may be crystalline and the form of the drug may be controlled by selection of the solvent used in the preparation of the formulation for coating (Codina, e.g., 0024). Like Kangas, Codina teaches crystalline form of the drug is desirable for sustained dosing and longer effect to achieve better therapeutic results with less probable restenosis (Codina, e.g., 0026). Codina teaches the drug having a small crystal size, e.g., in the range of nanometers (Codina, e.g., 0026). Codina teaches the triglyceride excipient, e.g., caprylic acid triglyceride, i.e., trioctanoylglycerol (Codina, e.g., claim 6) is effective to retain crystalline drug on the device while also promoting drug transfer to tissue at the treatment site (Codina, e.g., 0030-0035). 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 drug on devices (Codina, e.g., 0027) with excellent adhesion such that losses during navigation are very low (Codina, e.g., 0042).
It would have been obvious before the effective filing date of the presently claimed invention to modify coating suspensions containing microcrystalline limus drugs understood from Kangs by including a triglyceride excipient such as those of formula 1, e.g., trioctanoylglycerol known from Codina to improve the device coating formed using the suspension in the same way. The skilled artisan would have been motivated to make this modification for improved microcrystalline drug retention and improved drug to tissue transfer in the same way reported by Codina. The skilled artisan would have considered this modification the use of a known technique to improve similar coating compositions in the same way. The skilled artisan would have had a reasonable expectation of success since Kangas teaches the coating compositions may further comprise excipients such as triglycerides and since Codina teaches particular triglycerides which offer improved drug retention and improved drug tissue transfer.
Regarding the limitation of wherein the at least one tri-O-acylglycerol and the at least one limus active agent are present in a mass ratio of 10% - 30% tri-O-acylglycerol to 90% - 70% limus active agent: Codina teaches a coating formulation having mass ratio of 20 tricaprylin to 80 drug (Codina, e.g., 0053 and 0023). This is an example in the claimed ranges. The skilled artisan would have been motivated to start optimization using these amounts since Codina exemplifies these amounts as effective to achieve the reported improvements of drug adhesion and surface retention.
Regarding the limitation of wherein the solvent is a non-solvent having a dielectric constant er at 20°C of < 2.0 or the solvent mixture contains at least 50% by volume of a non-solvent having a dielectric constant er at 20°C of < 2.0.: Kangas clearly names heptane as a non-solvent for limus agents 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 for coat formulations suggested by Codina as a suspension in which the limus drug does not dissolve so that the drug remains in crystalline form for nucleating the applied coating as reported in Kangas.
As evidenced by the specification, trioctanoylglycerol is soluble in heptane (Spec, e.g., pg. 42:15-19).
Applicable to claims 4-5 and claim 1: 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.
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.
Claim 8 is included in this rejection as further limiting an optional solvent mixture limitation of claim 1. Further, Kangas teaches vehicles which may be effective to induce crystallization of the limus drug includes similar mixed solvents such as heptane/ethyl acetate (Kangas, e.g., 0065). This meets the mixed solvent limitations of claim 1.
Accordingly, the subject matter of claims 1-2, 4-6, and 8 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-2, 4-6, and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-6, and 8 of U.S. Ap. No. 18036665 in view of Kangas, US 20150250772.
The claims in this case and the copending case have been amended to recite substantially similar suspension formulations which differ only by the active agent. The particle size ranges, solvent, and tri-O-acylglycerol identity and ratio with the active are now the same.
The claims of the reference application teach a suspension for coating of a medical device selected from a catheter balloon, a balloon catheter, a stent, or a cannula, the suspension containing: a) at least one tri-O-acylglycerol selected from the group consisting of trioctanoylglycerol, trinonanoylglycerol, tridecanoylglycerol, and triundecanoylglycerol, b) at least one taxane active agent in the form of microcrystals having a crystal size of at least 1 µm, and c) a solvent or a solvent mixture in which the at least one tri-O-acylglycerol dissolves and in which the microcrystals of the at least one taxane active agent do not dissolve, wherein at least 90% of the at least one taxane active agent is in the form of microcrystals having a crystal size of at least 10 µm; wherein the at least one tri-O-acylglycerol and the at least one taxane active agent are present in a mass ratio of 10% - 30% tri-O-acylglycerol to 90% - 70% taxane active agent; wherein the solvent is a non-solvent having a dielectric constant er at 20°C of < 2.0 or the solvent mixture contains at least 50% by volume of a non-solvent having a dielectric constant er at 20°C of < 2.0.
The difference between the reference claims (taxane) and the present claims (limus) is the active agent.
Kangas teaches paclitaxel and analogs thereof (taxane) and rapamycin and analogs thereof (limus) were both known water soluble drugs used for inhibiting restenosis when delivered from a medical device surface (Kangas, e.g., 0028-0035).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify coating suspensions of the reference claims by including a limus active with a reasonable expectation of success. The skilled artisan may have seen this as a substitution of one known anti-restenosis drug for another to predictably arrive at a suspension of crystalline drug useful for coating medical devices effective to inhibit restenosis. Alternatively, the skilled artisan may have seen this modification as a combination of two known drugs useful for the same purpose to predictably arrive at a suspension of crystalline drug useful for coating medical devices effective to inhibit restenosis. See MPEP 2144.06. The results would have been predictable since Kangas suggests both drugs were known to form crystalline forms and were known for delivery from medical device surfaces as inhibitors of restenosis.
Accordingly, the subject matter of claims 1-2, 4-6, and 8 would have been prima facie obvious to one of ordinary skill in the art 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.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
/SUSAN T TRAN/Primary Examiner, Art Unit 1615
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