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 .
Election/Restrictions
Applicant’s election of Group I (claims 1-22) in the reply filed on 02/05/2026 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)). Specifically, Applicant has not clarified whether the restriction is made with or without traverse.
Claims 23-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim.
Furthermore, Applicant elects “suprachoroidal space” as the location for device insertion of the possible alternatives (e.g., anterior segment, posterior segment, vitreous humor, or suprachoroidal space) found in withdrawn claims 25-28.
Priority
The present application claims the benefit of Provisional US applications 63302292, 63436312 filed 01/24/2022, 12/30/2022, respectively.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 01/20/2023, in the matter of Application N° 18/157,123. Said documents have been entered on the record. The Examiner further acknowledges the following:
Claims 1-28 are pending.
Claims 23-28 are withdrawn from consideration as directed to non-elected inventions.
Claims 1-22 are presented for examination and rejected as set forth below.
Drawings
The drawings are objected to because Figure 5 is of poor resolution (as compared to Figure 6). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 12 is objected to because of the following informalities: misspelling “a” (with “aa”). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-6, 8-9, 13, and 17-21 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.
Claims 2-5, 8-9, 13, and 17-21 recite the term “about” to describe numerical values, which is indefinite because it is an imprecise definition of a value, which is not further defined in the Application (e.g., the Specification does not provide a definition that provides consistent interpretation of the term). The Examiner suggests “about” should be removed and considers the claim values as if the term “about” was not present. See MPEP 2173.05(b)(i).
Claim 6 is considered indefinite for using the transitional term “includes” but providing a closed list, such that it represents an open-ended improper Markush grouping. See MPEP 2173.05(h). The Examiner recommends using “selected from the group consisting of” or “is” or something similar. In this situation, it would be inappropriate to claim the “tyrosine kinase inhibitor” (TKI) of claim 6 (i.e., this term ordinarily represents a TKI compound or combination of TKI compounds) “includes” (i.e., comprises) other excipients and/or non-tyrosine kinase inhibitor actives, for example. Note: the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("[L]ike the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended.").
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, 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.
Claims 1-2, 6-12, 15, and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US 5443505), and in further view of Blizzard (WO2021195163A1) and Zarnitsyn (US20150258120A1).
Applicant’s claims are directed to an implantable device comprising a core that defines an outer peripheral surface, wherein the core comprises a core polymer matrix within which is dispersed a tyrosine kinase inhibitor (TKI), the polymer matrix containing an ethylene vinyl acetate copolymer. In the BRI, having the “core that defines an outer peripheral surface” as stated in claim 1, encompasses a monolithic object, because the core reaches the outer peripheral surface.
Although the categories claimed are interpreted by their BRI (i.e., the categories of “hydrophilic compound” of claim 10 and “water-soluble particle” of claim 16 can cover a broad range of materials), examples of these terms are considered in Applicant’s Specification to understand Applicant’s intent of meaning. Thus, the Specification includes examples of “hydrophilic compounds” such as alginates, gelatin etc. [0026] and examples of “water-soluble particles” as hydroxy-functional ingredients such as monosaccharides, disaccharides, sugar alcohols, etc. as non-limiting examples [0028]. Further note that a chemical species and its properties are inseparable.
Wong teaches eye implants comprising active agents for treating eye conditions (including macular degeneration in col 9, last paragraph) in a controlled release fashion into the suprachoroidal space (abstract, Wong- claim 1).
Regarding claim 1: Wong teaches an implant, where an active agent (i.e., drug) is dispersed in biocompatible, non-biodegradable polymers (col 3, lines 35-46) such as ethylene vinyl acetate (EVA) copolymer (col 3, lines 64-70; col 4, lines 1-15). Furthermore, Wong teaches drug-loaded implantable eye devices, that may employ “any pharmacologically active agent for which sustained release is desirable” (see col 8, lines 27-70), including agents for macular degeneration (col 9, last paragraph).
Regarding claim 2: Wong teaches the active agent as 20-40 wt% (col 9, lines 4-46).
Regarding claims 7-9: The implants may also be of any geometry including fibers, sheets, films, microspheres, circular discs, plaques and the like, and in the case of fibers (which have circular cross sections and a linear length, and are thus, cylindrical in shape), the general size is a diameter of 0.1-1 mm by a length of 0.5-5 mm (col 10, lines 11-30), wherein with regard to the numerical range, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (see 2144.05(I)). See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”).
Regarding claim 10: Wong teaches incorporation of gelatin, silicones (col 3, lines 35-46), alginates, different celluloses, polyvinyl alcohols, (col 5, lines 35-46), etc., which are recognized by Applicant’s Specification as suitable hydrophilic compounds [0026].
Regarding claim 11-12: Wong teaches surrounding membranes (in addition to monolithic structures) that can control release of the drug (col 7, lines 57-69). Wong teaches the membrane may be composed of any of the biocompatible materials indicated above (in the disclosure) and may vary with the drug employed, and thus, EVA would be selected (col 4, lines 48-70).
Regarding claim 15: There is no requirement for the drug to be in a membrane layer, whereby a membrane is affixed to the polymer layer comprising the drug (col 4, lines 48-70).
Regarding claim 17: Wong teaches 10 mg of drug loading (col 14, lines 58-70).
Regarding claim 18-21: Wong teaches eye implantation between at least 2 weeks (14 days) to 8 weeks (about 2 months). However, 6 months or more of implant is possible (col 6, lines 57-70) (thus, the release period of 6 months or more overlaps with the instant release period of 12 months or more).
Regarding claim 22: Wong teaches release of therapeutic drug levels in the eye (col 17, lines 35-53).
In summary, Wong teaches an implantable eye device suitable for various types of drug active agents, including “any pharmacologically active agent for which sustained release is desirable may be employed” (see col 8, lines 27-70, and col 9, lines 1-40), including active agents for macular degeneration (col 9, last paragraph), and also comprising EVA. However, Wong does not teach specifically tyrosine kinase inhibitors (TKIs) (instant claims 1 and 6).
Blizzard teaches ocular implant, containing a dispersed tyrosine kinase inhibitor (TKI) for sustained release delivery (abstract), and names specifically axitinib, gefitinib, imatinib, etc. (line item #25 on pg 77) (reads on axitinib, gefitinib, imatinib, etc. of instant claim 6). These TKIs can be used in combination with synthetic polymers (without limitation) [00148] for various types of implantation administration (including suprachoroidal) [00334]. The implant can be cylindrical and size is 0.3-0.4 mm [000213]. Blizzard teaches there is an urgent need for an improved treatment of ocular diseases such as AMD, DME, and RVO with TKIs, which is effective over an extended period of time avoiding the need for frequent (monthly or even daily) injections which are currently required for common anti-VEGF therapies, especially for individuals not responding to anti-VEGF therapies (e.g. up to 33% of subjects with DME) [00013].
Zarnitsyn teaches injections into the suprachoroidal space for macular degeneration [0298], that can comprise implants [0216] and tyrosine kinase inhibitors (TKI) [0177-0178] such as axitinib, imatinib, etc. [0192].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the drug-loaded cylindrical ocular implants taught by Wong by selecting a tyrosine kinase inhibitor as the drug, as taught by Blizzard, because Blizzard teaches TKI-loaded implants as effective formulations to provide sustained release of medication to treat disease such as macular degeneration such as AMD [00012-00013]; Zarnitsyn teaches injections into the suprachoroidal space for macular degeneration [0298], that can comprise implants [0216] and tyrosine kinase inhibitors (TKI) [0177-0178] such as axitinib, imatinib, etc. [0192]; and Wong teaches drug-loaded implantable eye devices, that may employ “any pharmacologically active agent for which sustained release is desirable” (see col 8, lines 27-70), including agents for macular degeneration (col 9, last paragraph). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Blizzard and Zarnitsyn also provide motivation to incorporate TKIs (i.e., useful for macular degeneration) into the implants of Wong (that incorporate active agents to treat macular degeneration), because Blizzard teaches there is an urgent need for an improved treatment of ocular diseases such as AMD, DME, and RVO with TKIs, which is effective over an extended period of time avoiding the need for frequent (monthly or even daily) injections which are currently required for common anti-VEGF therapies, especially for individuals not responding to anti-VEGF therapies (e.g. up to 33% of subjects with DME) [00013].
Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US 5443505), Blizzard (WO2021195163A1) and Zarnitsyn (US20150258120A1), as applied to claims 1-2, 6-12, 15, and 17-22 above, and in further view of Garcia-Estrada (Pharmaceutics, 2021), Govender (Advanced Drug Delivery Reviews, 2021), De Nijs (US4957119A) and Thakur (WO2020128062A1).
As discussed above, Wong and Blizzard teach a tyrosine kinase inhibitor (TKI) drug-loaded cylindrical implant, comprising EVA. Note that Wong generally teaches incorporation of “other agents” including enhancers that affect the rate of drug delivery (col 9, lines 47-70), and that rate of release (e.g., by diffusion) is governed by polymer properties, such as cross-linking, hydrophilicity, etc. (col 4, lines 49-70). However, the Prior Art does not teach the EVA monomer ratio (instant claim 3, 13-14), melt flow index (instant claim 4), melting temperature (instant claims 5), nor the water-soluble (hydrophilic) particle (instant claim 16) (where the categorical term is understood using examples of the Specification, as previously discussed in the claim interpretation section above).
Garcia-Estrada teaches common non-biodegradable materials for drug eye implant formulations to treat eye disease (abstract). Garcia-Estrada teaches EVA is a transparent thermoplastic, ethylene monomer copolymer (Figure 3) that normally contains from 1 to 40% of vinyl acetate (VA) monomer (overlapping with the instant vinyl acetate monomer content of 10-60 wt% in claim 3, 13-14). Depending on the percent of VA, EVA may take different physical properties; the more VA, the higher polarity, adhesion, impact resistance, flexibility, and compatibility with other polymers. However, when increasing VA, a decrease in crystallinity, stiffness, softening, and melting point is also observed, as exemplified in Tables 1 and 2 [20,21], where the melting points of 60 °C is known (reads on instant claim 5). Thus, knowing that EVA properties are impacted by monomeric amount, one would modulate monomeric content based on desired property of the core and membrane, thus making claim 14 obvious. Garcia-Estrada also teaches a cylinder as a common shape for eye implants (Table 6).
Govender teaches melt flow index (‘rheological techniques’, Table 4) and melting temperature (‘thermal techniques’, Table 4) as a fundamental tool to measure rheological properties of polymers (Table 4) such as ethylene vinyl acetate when used in solid dispersions (Table 2). Thermal properties and rheological properties are inter-related and important for both the process or making and the final product properties (pg 20-21), including pharmaceutical products (abstract, Fig 3), whereby the polymer physical properties modify the drug release rate of dosage forms (pg 11).
De Nijs teaches drug-loaded implants made of an EVA core with an EVA membrane (abstract). De Nijs teaches a cylindrical implant with a melt-flow index of the core is greater than 10 gram per 10 minutes (reads on instant claim 4), and a vinyl acetate content of 20% by weight or more; and the membrane has a melt index is less than 10 gram per 10 minutes (reads on instant claim 4), and an acetate content of less than 20% by weight (col 2, lines 1-26). This particular configuration allows for a release system that combines a core of active material with a release-rate regulating membrane (col 1, lines 50-58).
Thakur teaches drug release modulating excipients such as glucose, lactose, mannitol (Thakur – claims 8-9, pg 12-13), as applied as excipients within solid eye implants (pg 1).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cylindrical implant comprising a TKI taught by the combined Prior Art with the specific EVAs and EVA properties taught by Garcia-Estrada, Govender, and De Nijs, because these EVAs are useful for eye implant devices, and specifying the makeup or properties of the EVA in the device can modulate drug release rates. Furthermore, Wong teaches that rate of release (i.e., by diffusion) is governed by polymer properties, such as cross-linking, hydrophilicity, etc. (col 4, lines 49-70), and thus it would make sense to alter the drug rate of release in Wong’s implants by chemically modifying the polymer (as described by Garcia-Estrada, Govender, and De Nijs) to alter the polymer properties and therefore, modify drug release rate. Additionally, Estrada, Govender, and De Nijs collectively establish EVA monomer ratio, melting point, and melt flow index, as a result-effective variables, that a person of ordinary skill in the art would routinely optimize in order to improve release rate. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (indicating that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation).Thus, a PHOSITA would seek to optimize the EVA properties and monomer ratio (of both the core and the membrane) in search of the desired properties of the drug-device product, such as drug release rate.
As far as the ASTM protocols of claims 4 and 5, it should be noted that the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise. “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cylindrical implant comprising a TKI taught by Wong and Blizzard with the release modulating excipients of glucose, lactose, mannitol, as taught by Thakur, because Thakur teaches these ingredients as useful release modulating excipients for solid eye implants (‘summary of invention’), where Wong teaches modulation of active agent release in a controlled release fashion into the suprachoroidal space (abstract, Wong- claim 1; col 3, lines 20-34) by implant/membrane structure (col 4-5), polymer choice (col 4, last paragraph), various agents (col 9, lines 47-70), etc.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Cao (Drug Discov Today, 2019).
Cao teaches monolithic ocular implants for sustained release, where design includes material selection, API, and implantation site (abstract).
Regarding claim 1: Cao teaches EVA as a commonly used nondegradable material for ocular drug delivery implant (pg 3, paragraph 1). Cao also teaches TKIs for ocular implant (pg 4, paragraph 1), where the drug is suspended (i.e., dispersed) within the polymer for sustained delivery (pg 4). The implant is monolithic (reads on “core that defines an outer peripheral surface”) (abstract).
Thus, instant claim 1 is taught as obvious by Cao.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over, and in further view of Blizzard (WO2021195163A1) and Cao (Drug Discov. Today, 2019):
claims 1-8, 19, 21-29, and 31-35 of copending Application No. 17/982,556 (reference application)
Although the claims at issue are not identical, they are not patentably distinct from each other because all claim sets teach an implantable device for eye implant comprising an ethylene vinyl acetate copolymers. The copending application differs only significantly by incorporating a steroid agent instead of the tyrosine kinase inhibitor (TKI) of the instant claims.
This is remedied by Blizzard, who teaches eye implants comprising specific TKIs for treatment of disease (abstract, pg 77), including treatment of ocular inflammation [0134]. Cao also teaches TKIs for ocular implant (pg 4, paragraph 1), where the drug is suspended (i.e., dispersed) within the EVA polymer for sustained delivery (pg 4). One of ordinary skill in the art would have been motivated to modify the teachings of copending application ‘556 by substituting the steroid for the TKI because both active agents are useful for treating ocular inflammation, with the device formulation remaining essentially the same otherwise.
This is a provisional nonstatutory double patenting rejection.
Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-27 of copending Application No. 18/157,134 (reference application)
Although the claims at issue are not identical, they are not patentably distinct from each other because all claim sets teach basically the same invention (i.e., eye implant comprising a TKI) except the copending application contains slight variations of the instant device (e.g., incorporation of an additional steroid active agent, etc.).
Thus, the copending application claim set teaches the limitations of the instant claim set.
This is a provisional nonstatutory double patenting rejection.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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/R.P./Examiner, Art Unit 1614 5/14/26
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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