DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 4 September 2025 has been entered, and the arguments presented therein have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112(a) – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6, 8-10, 14-18, 20-24, 27-34, 37-39, and 41-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims have been amended to require that the implant is substantially rod-shaped. This does not appear to be adequately supported by the original application as filed.
In contrast, the instant application discloses that the implants are “generally rod-shaped.” See the instant specification on page 10, paragraph 0042. This does not appear to adequately support the claim requirement that the implants be “substantially rod-shaped” as it is not clear that the term “generally” in the specification provides adequate support for the claimed term “substantially.”
In order to overcome this rejection, the examiner suggests that the term “substantially” be removed and replaced with “generally.”
Claim Interpretation
Micelle-Forming Active Agents: The examiner further takes the position that the term “saline” in claim 22 is understood to refer to salt water wherein the salt is NaCl. It is not understood to refer to a solution of surfactant in water. This is particularly relevant because a drug that forms surfactant-containing micelles when mixed into an aqueous solution comprising surfactant but does not form micelles when mixed into saline (lacking surfactant) is not understood to read on the claimed invention.
As best understood by the examiner, paclitaxel is a drug frequently used in implants. For example, as best understood by the examiner, paclitaxel (that has not been derivatized) would not have formed micelles when combined with saline (in the absence of surfactant) and therefore would not have read on the requirements of the lipophilic pharmaceutical substance of claim 22.
See the instant specification on pages 12-13, paragraphs 0058-0061 for a description of what substances are micelle-forming substances.
Relevant Prior Art – No Rejection
The examiner has cited prior art below that is relevant to the claimed invention, but over which no rejection has been written. The examiner has explained why no rejection has been written over the below-indicated prior art.
Tagliaferri Reference: As relevant prior art, the examiner cites Tagliaferri et al. (US 2011/0190688 A1). Tagliaferri et al. (hereafter referred to as Tagliaferri) is drawn to Tagliaferri et al. (hereafter referred to as Tagliaferri) is drawn to a permeant delivery system, as of Tagliaferri, title and abstract. Tagliaferri teaches a drug delivery device comprising EVA (ethylene vinyl acetate) and mannitol, as of Tagliaferri, paragraph 0162. This appears to be used to deliver an active agent. Elsewhere in the document, Tagliaferri teaches Paliperidone palmitate in a long list of drugs, as of Tagliaferri, paragraph 0088; this appears to be a lipophilic/amphiphilic pharmaceutical substance.
Nevertheless, Tagliaferri does not teach that the composition is substantially rod-shaped or generally rod-shaped. In fact, the device of Tagliaferri is in the form of a patch, as of at least paragraph 0039 of Tagliaferri, which would not have been considered substantially or generally rod-shaped. The skilled artisan would not have been motivated to have modified the device of Tagliaferri to have been rod-shaped because the skilled artisan would have expected that such a modification would not have been useful for transdermal delivery, which is the intended use of the device of Tagliaferri. This is because the skilled artisan would have expected that a generally rod-shaped structure would have provided less contact of the drug delivery device with the skin and therefore would have resulted in worse transdermal delivery as compared with the patch shape of Tagliaferri. If a proposed modification would render the prior art invention being modified unsatisfactory for its intended purpose, there may be no suggestion or motivation to make the proposed modification. See MPEP 2143.01(V). Additionally, the mere fact that references can be combined or modified does not render the resultant combination obvious unless the results would have been predictable to one of ordinary skill in the art. See MPEP 2143.01(III).
Ross Reference: The examiner further notes that the file record includes prior art drawn to microneedles for transdermal delivery. See interview summary added to the file record on 27 June 2024, specifically citing Ross (CN 102639184 A1). The microneedles of Ross have the following structure.
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As an initial matter, the skilled artisan would not have understood microneedles to have been substantially rod-shaped because the point at the end of the microneedle would not have been considered by the skilled artisan to have been part of a rod. In contrast, the skilled artisan would have understood that the general shape of a rod would have comprised approximately equal thicknesses at both ends. This is evident as of Fujioka et al. (US Patent 5,851,547), which teaches a cylindrical rod form, as of the title, abstract, and figure 1, reproduced below.
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This differs from the composition of Ross because it appears to have a constant diameter throughout the length of the rod, whereas in the case of Ross, the diameter is not constant across the length of the rod. Also see Winter et al. (US 2011/0059140 A1), which teaches the following, as of paragraphs 0091-0092, reproduced below.
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The structure of Ross, in contrast to that of Winter, does not have a defined diameter because the diameter changes with length. As such, the skilled artisan would not have considered the composition of Ross to have been generally rod-shaped.
Nevertheless, even if, purely en arguendo, microneedles are understood to have been rod-shaped, the skilled artisan would not have been motivated to have combined Ross with Tagliaferri. This is because the composition of Ross appears to operate by a different principle of operation as compared with the claimed invention. In support of this position, the examiner cites applicant’s response on 15 January 2025, relevant text reproduced below.
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The examiner agrees with applicant’s general conclusion that the skilled artisan would not have been motivated to have combined Tagliaferri with Ross. The proposed modification (of a reference combination) cannot change the principle of operation of the reference. See MPEP 2143.01(VI). In this case, were Ross to be combined with Tagliaferri, the principle of operation of Tagliaferri would have been changed; as such, the examiner takes the position that a combination of Ross with Tagliaferri is not appropriate.
Crowley Reference: Previously in the prosecution history, the examiner cited Crowley et al. (US 2009/0264385 A1). Crowley et al. (hereafter referred to as Crowley) is drawn to a bioadhesive composition, as of Crowley, title and abstract, apparently for buccal administration, as of Crowley, paragraph 0002. The examiner previously noted that Crowley teaches that the composition can be in the form of cylinders, as of paragraph 0090 of Crowley. However, it appears that these cylinders are an intermediate product rather than the final product, as this appears to be the shape of the molten blend prior to cooling. Furthermore, Crowley does not teach a non-biodegradable matrix. The examiner notes that Crowley teaches mannitol nitrate, as of Crowley, paragraph 0200. While mannitol is a sugar alcohol, it appears that Crowley intends mannitol nitrate as the active agent itself; therefore, the skilled artisan would not have been motivated to have included mannitol nitrate with an additional active agent that has the properties required by the instant claims.
Spada Reference and Biodegradable Implants: The examiner further notes that are multiple prior art references drawn to rod-shaped implants for drug delivery. As representative of this genus of prior art references, the examiner cites Spada et al. (US 2010/0124565 A1). Spada et al. (hereafter referred to as Spada) is drawn to a biocompatible intraocular implant, as of Spada, title and abstract. The drug intended to be delivered by Spada is brimonidine. The implant of Spada may be in the shape of a rod, as of Spada, paragraphs 0055 and 0093.
Nevertheless, the implants of Spada are biodegradable, and therefore differ from the claimed invention which is an implant comprising a non-biodegradable matrix which comprises a non-biodegradable polymer. See the title of Spada, which teaches the term “biodegradable.” Additionally, the implants of Spada are made from polylactic acid (PLA) or a copolymer of polylactic and polyglycolic acids (PLGA), as of Spada, paragraph 0088. There would have been no motivation for the skilled artisan to have modified the implant of Spada to have substituted a non-biodegradable polymer in place of the PLA/PLGA of Spada. This rationale would appear to apply to prior art cited by Spada, e.g. as of paragraphs 0009-0010 of Spada, all of which are drawn to biodegradable implants made from PLA.
Comparative Testing: The instant specification contains comparative testing of the claimed composition as compared with a comparative example lacking the sugar alcohol. This comparative testing is presented as of page 28, Example 4, which is reproduced below.
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The above-reproduced data would appear to show that the use of mannitol, which is a sugar alcohol, would appear to improve the extraction efficiency of the active agent liraglutide when combined with the polymer EVA. This is as compared with a comparative example wherein liraglutide was combined with EVA in the absence of mannitol. The above-reproduced data also indicates that the use of mannitol would appear to overcome problems that would have occurred due to the active agent having been lyophilized. This would appear to improve the ability of the required components to be stored prior to being formulated without losing the ability of the claimed composition to operate properly.
Brem Reference: As relevant prior art, the examiner cites Brem et al. (US Patent 5,626,862). Brem et al. (hereafter referred to as Brem) is drawn to a composition for delivery of a chemotherapeutic agent. Brem teaches ethyl vinyl acetate implant, which is non-biodegradable, as of at least figure 4 of Brem (though the examiner notes that the non-biodegradable implant is not the most preferred implant of Brem). Brem teaches cylinder on column 24 lines 40-45. Teaches mannitol as a disintegrant on column 10 lines 10-17.
Brem does not teach the required lipophilic pharmaceutical substance required by claim 1. The examiner notes that Brem exemplifies camptothecin and paclitaxel as pharmaceutical substances. These active agents would not have read on the required lipophilic pharmaceutical substance which is a lipid conjugated to a pharmaceutical substance, as required by claim 1. These active agents would not have been “amphiphilic” as required by claim 24. The term “amphiphilic” implies the presence of both a hydrophobic and a hydrophilic region, and neither camptothecin nor paclitaxel have the required hydrophilic region and thus cannot be considered amphiphilic. Additionally, there is no evidence that camptothecin or paclitaxel would have been able to have formed micelles in saline in the absence of a surfactant, as required by claim 22. Brem also teaches other active agents as of column 9 lines 1-21, including small molecules such as novobicin as well as proteins such as IL-6. There is no indication that these drugs would have met the requirement of instant claim 1 of being a lipophilic pharmaceutical substance, of instant claim 22 of forming micelles in saline, or of instant claim 24 of being amphiphilic.
Even if, purely en arguendo, the skilled artisan would have been motivated to have combined the ethyl vinyl acetate polymer of Brem, the mannitol of Brem, and the cylinder shape taught by Brem, and to have substituted a “lipophilic pharmaceutical substance” in place of the active agents of Brem, there would have been no evidence that the resultant formulation would have achieved the unexpected results achieved in the instant application. As explained above, the instant specification discloses that mannitol improves extraction and lyophilization stability. There would have been no evidence that this unexpected improvement would have occurred in Brem.
The examiner additionally notes that Brem teaches the following regarding the use of mannitol, as of Brem, column 10, relevant text reproduced below.
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The above-reproduced text would appear to motivate the skilled artisan to have added mannitol only in the case wherein the formulation also comprises binding materials. A hypothetical ethyl-vinyl acetate implant comprising only ethyl-vinyl acetate and active agent would not have comprised binding materials; as such, the skilled artisan would not have been motivated to have added mannitol to such an implant.
Conclusion
No claim is allowed at this time.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Frederick F Krass can be reached at (571)272-0580. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612