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 the PBAE of “Formula I” described in Claim 4 wherein R is “B5,” R’ is “S3,” and R” is a propyl-N-piperazine-N-propylamine moiety, as well as a gene as the active, and Stargardt disease as the condition to be treated in the reply filed on 4 June 2026 is acknowledged. As applicants have not identified any particular substituent for variables R1-R9, the examiner has concluded that hydrogen substituents have been elected for these variables. 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)).
Status of the Claims
Claims 1, 4-16, and 18-32 are pending.
Claims 5-7, 10, 21, and 27-29 are withdrawn from consideration as directed to non-elected inventions.
Claims 1, 4, 8, 9, 11-16, 18-20, 22-26, and 30-32 are presented for examination and rejected as set forth below.
Priority
The instant application is a Continuation of earlier application 16/753,245 filed 20 April 2020, which is a National Stage entry of International application PCT/US2018/053990 filed 2 October 2018, which claims the benefit of Provisional U.S. application 62/567,043 filed 2 October 2017.
Claim Interpretation
Applicants Claims and 32 are directed to methods of treating ocular diseases by the suprachoroidal injection of nanoparticle or microparticle compositions containing therapeutic agents and a PBAE or PEG-PBAE copolymer. Dependent claims 4, 8, 9, and 11 narrow the biodegradable polymer to the poly beta amino ester described above. Claims 12, 19, and 20 indicate that the composition is formulated to “spread after delivery…and uniformly distribute and localize in a region of the suprachoroidal space, and wherein the nanoparticle or the microparticle localizes to a cell type.” Applicants do not provide a guiding definition for what is meant by “uniformly distribute and localize in a region,” or “localizes to a cell type”; any composition designed to distribute and remain in contact with the cells in question will be deemed to satisfy these claim limitations. Claim 13 requires the addition of a carrier component, with Claims 14-16, 18, and 22-26 specifying the type of active agent to be included in the composition, or the disease to be treated. Claim 30 requires that the composition be administered twice; applicants are reminded that simply duplicating steps has no patentable significance unless a new and unexpected result is produced. In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960). Claim 31 defines a per kilogram dose range of the composition of Claim 1 to be administered.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 8, 9, 11-16, 18-20, 22-26, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Green (WO2010/132879) in view of Prausnitz (U.S. PGPub. 2012/0226260), Buchlis (U.S. PGPub. 2016/0346359), and Wubben (Thomas J. Wubben, et al, Retinal Neuroprotection: Overcoming the Translational Roadblocks, 192 Am. J Ophthalmol. 15 (2018) (all of record).
Green describes biodegradable polymers designed to self-assemble with DNA to form particles effective for gene delivery. (Abs.). Green indicates that these compositions are designed to be useful in the treatment of, among others, ophthalmic diseases. (Pg.4, L.14-21). Each of the microparticles and nanoparticles of the instant claims are recited as suitable forms for the polymer to be used in. (Pg. 5, L.5-6). Of particular interest to the instant claims, as well as the species applicants have elected to represent the biodegradable polymers of the instant application, are the compounds of formula (I), which are the compounds of formula (I) of the instant Claims. (Pg.11). Concerning the species elected by applicants, Green indicates, as applicants have elected for the particular species for the instant application, variable substituent R” may be a propyl-N-piperazine-N-propylamine moiety. (Pg.18). The identical R group “B5” applicants have elected is identified by Green as a preferred diacrylate substituent R, as is the elected 3-amino-1-propanol substituent S3 for variable R’. (Pg.15; 62; 64). Green therefore suggests the species of polymer of formula (I) elected by applicants. Green indicates that these biodegradable cationic polymers are suitably combined with small molecules, DNA, RNA and the like for use in treating ophthalmic diseases such as, yet not limited to, age-related macular degeneration. (Pg. 22, L.25-34). While Green is silent as to the dosage of the polymer/therapeutic agent composition to be used to treat ophthalmic diseases, Green does specify that these are therapeutic compositions designed to be administered in “effective amounts” to treat any of variety of diseases, including ophthalmic diseases. (Pg.36, L.21-26). A person of ordinary skill in the art would reasonably have expected that the amounts of each, are result-effective variables that achieve the results each of the components referred to provide. As such, it would have been routine to optimize the amounts of these components within the total composition suggested by Green. 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.). As applicants have not presented evidence tending to establish the criticality of the particular dosages recited by Claim 31, these are an obvious permutation of the teachings of Green.
Green, despite teaching the sue of the instantly claimed cationic biodegradable polymers as usefully formed into micro or nanoparticle compositions for use in treating ophthalmic disorders, does not specify the localized administration of such a composition to the suprachoroidal space, nor is the use of a gene, or the treatment of Stargardt disease described.
Prausnitz describes the targeted administration of drugs to the suprachoridal space to provide for targeted delivery of therapeutic agents. (Abs). In particular, Prausnitz describes injecting a microneedle into the sclera of the eye and subsequently infusing a drug formulation into the suprachoroidal space of the eye to provide for both extended delivery times as well as increased bioavailability of drug formulations so infused. [0028-31]. Prausnitz indicated that a wide variety of ocular diseases and disorders may suitably be treated by the methods described, including but not limited to genetic diseases of the eye, for example by the infusion of fluid drug formulations designed to deliver selected DNA, RNA, or oligonucleotides to targeted ocular tissues. [0034]. In this manner, Prausnitz indicates that cells including each of the scleral, choroidal, and retinal pigment epithelial cells of Claim 20 can be targeted for delivery of the therapeutic agents so formulated. [0035]. Prausnitz describes a particular embodiment where nanoparticles or microparticles containing the active agent are injected to deliver the therapeutic agents to the eye for delivery to the particularly targeted tissues. [0049; 0077-81].
Buchlis describes methods of treating genetic disorders of the eye including Stargardt disease of the instant claims. [0004; 0060 “Table 1”]. Treatment in this manner is accomplished by the use of a nucleic acid sequence encoding a CRISPR-Cas9 system for targeted gene correction. [0006-07]. Ocular and retinal cells are described as suitably targeted by such systems for tissue-specific expression control. [0026]. Genes to be targeted by such systems include VEGF for age-related macular degeneration and each of, among others, the instantly claimed RPGR as well as RPE65. [0060: “Table 1”]. Wubben establishes that retinal neuroprotection is broadly defined as any measure that reduces the death of retinal cells or axonal extensions into the optic nerve, as well as the fact that therapies designed to restore the function of mutated RPE65 genes which Buchlis recites as a target for modulation are known to be effective in reducing retinal cell death. [xv-xvii]. As such, the skilled artisan at the time of the instant application, in targeting the RPE65 gene or for treatment of Stargardt disease would necessarily have utilized a gene which is neuroprotective to the retina as is required by Claim 29. Buchlis indicates the suitable CRISPR-Cas9 constructs are to be provided as plasmids for delivery to the tissues to be targeted.
It would have been prima facie obvious for a skilled artisan at the time of the instant application to have employed the biodegradable PBAE polymer microparticles or nanoparticles in combination with a DNA or RNA sequence for treatment of ophthalmic diseases such as age-related macular degeneration disclosed by Green in the methods of suprachoridal delivery described by Prausnitz to arrive at the subject matter of the instant claims. One having ordinary skill in the art would have been motivated to do so because Prausnitz suggests the targeted delivery of nanoparticle or microparticle containing fluid compositions via injection into the suprachoroidal space to target the delivery of the therapeutic compositions to the sclera, choroid, or retinal pigment epithelium encompassed by the instant claims for the treatment of any ophthalmic disease, but specifically reciting each of genetic diseases of the eye as well as macular degeneration. Utilizing the biodegradable PBAE microparticles or nanoparticles and nucleic acid therapeutic agents described by Green in this context appears to amount to little more than the predictable use of prior art elements according to their established functions, and obvious thereby. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Furthermore, it would have been prima facie obvious to have selected any of VEGF, RPGR, or RPE65 as genes to be targeted by the administration of a suitable CRISPR-Cas9 plasmid to restore the function of mutated genes in either age-related macular degeneration or retinitis pigmentosa by targeted delivery through suprachoridal injection of a PBAE microparticle or nanoparticle containing fluid designed to target any of the choroid, sclera, or retinal pigment epithelia. One having ordinary skill in the art would have been motivated to do so because, as set forth above, Prausnitz suggests the targeted delivery of nanoparticle or microparticle containing fluid compositions via injection into the suprachoroidal space to target the delivery of the therapeutic compositions to the sclera, choroid, or retinal pigment epithelium encompassed by the instant claims for the treatment of any ophthalmic disease, but specifically reciting each of genetic diseases of the eye as well as macular degeneration. Utilizing the biodegradable PBAE microparticles or nanoparticles and nucleic acid therapeutic agents described by Green in this context appears to amount to little more than the predictable use of prior art elements according to their established functions. Adding to this is the fact that Buchlis explicitly identifies each of the VEGF and each of RPGR, or RPE65 of the instant claims as suitable targets for the treatment of age-related macular degeneration on the one hand, and retinitis pigmentosa on the other. As each of Prausnitz and Green envisage utilizing the compositions and methods of their disclosures to treat macular degeneration and other genetic disorders of the eye by the targeted delivery of nucleic acid therapeutic agents, the instant claims appear to be little more than the predictable use of prior art elements according to their established functions, and obvious thereby. See KSR, supra.
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.
At least Claims 1, 4, 8, 9, 11-16, 18-26, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,883,541. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘541 patent anticipate the claims of the present application.
Conclusion
No Claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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