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 with traverse of Group I where the amphiphilic polymer is polyethylene glycol-b-poly(hydroxylpropylmethacrylamide-oligolactate) and the nanoparticle surface comprises a glycoprotein targeting moiety that comprises boronic acid in the reply filed on January 5, 2026 is acknowledged. The traversal is on the grounds that the presence of parts of the copolymer of claim 49 in separate references in not an indication that the polymer fails to meet the criteria of a special technical feature. This is not found persuasive because the discussion of lack of unity showed the obviousness of the common technical feature and did not merely highlight parts of the claimed polymer in separate references. The evidence showing the absence of a contribution over the prior art in a common technical feature is not required to reside in a single reference. Sant et al. (previously cited) teaches a diblock copolymer in accordance with instant claim 49, with the exception of the presence of a boronic acid moiety on the hydrophilic block. The polymer self-assembles in water into micelles such that its polyethylene glycol (PEG) blocks form the shell/surface of the micelle. These micelles were explored as carriers for poorly water soluble drugs. Huang et al. then shows that the prior art recognized the utility of placing a boronic acid moiety at the end of the PEG block of a similar micelle forming diblock copolymer that was also employed to deliver drug with the added benefit of conferring targeting capabilities. As provided by Nagarajan et al. and Mahou et al. (previously cited), Prior art also already recognized how to attach such a moiety to the terminal group provided in the polymer of Sant et al. Thus the claimed polymer was not new, the concept and configuration of its terminal group was not new, and the chemistry to place it on the polymer also was not new. Therefore the instantly claimed polymer does not make a contribution over the prior art because it would have been obvious to make in light of the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claim 10 recites R2 as “optionally substituted alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl”. It is not clear how the elected substituent containing an isopropyl bound to oligolactate is embraced by this listing. In addition, claim 17 recites R1 as “hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl" with no mention of substitutions. Thus boronic acid containing substituents are not embraced and the elected polymer is not within the scope of claim 17 or its dependent claim 18.
Claims 17-18, 49-50, 52, and 54-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Drawings
The drawings are objected to because figure 4 is not legible. 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 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 10, 13-14, 26, and 30 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 10 recites R2 as “optionally substituted alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl”. The layered definition of the terms ”substituted” and “substituent” where each substituent could itself be substituted make the boundary on the permissible moieties unclear because it is difficult to discern which chemical moieties are included. For the sake of compact prosecution and the application of prior art, the elected polymer will be interpreted as fulfilling a substituted alkyl for this moiety. Clarification is still required.
Claim 13 recites a graphic representation of the hydrophobic block with a variable subscript “p” that is undefined. Thus the scope of the claim is unknown.
Claims 13 and 14 recite “the hydrophobic block”; however they depend from claim 3 which recites embodiments with one or two hydrophobic blocks. Thus it is unclear if the further limitation on “the” hydrophobic block applies to all the hydrophobic blocks that are present or just one of them.
Regarding claim 26, the term "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 30, the term "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
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 1-3, 6, 8, 10, 13-14, 21, 26-27, 30, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Soga et al. (Langmuir 2004 20:9388-9395) in view of Zhao et al. ( ACS Applied Materials and Interfaces 2016 8:14845-14854), Du et al. (Journal of Polymer Research 2011 18:753–762), and Fan et al. ( Marine Drugs 2019 17(285):1-14).
Soga et al. teach degradable thermosensitive polymer micelles for delivery of hydrophobic drugs, particularly for tumor and inflammation treatment (see abstract and page 938 second column and figure 1; instant claims 1 and 27). Paclitaxel is explicitly envisioned as an anti-cancer drug for inclusion (see page 9395 second column first full paragraph). The polymer is a diblock copolymer of poly(ethylene glycol) (PEG) and poly(hydroxypropylmethacrylamide-oligolactate) (pHPMA-DL), where the oligolactate polymer has 2 units of lactate as shown below:
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(see Scheme 1; instant claims 3, 6, 10, and 13). According to the instant nomenclature, Y = NH, R3 = alkyl, R2 = substituted alkyl (see instant claim 10). They detail the polymerization as the product of the PEG macroinitiator
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reacted with hydroxypropylmethacrylamide dilactate (see scheme 1). Soga et al. teach the number average molecular weight of the PEG block as 5000 Da while the pHPMA-DL block is 3000 Da, 6900 Da or 13,600 Da (see page 9389 second column first partial paragraph, and table 1; instant claims 6, 8, and 13-14). According to the instant nomenclature, these sizes correspond to n ≈ 24, 48, or 114, respectively (see instant claims 6 and 13). The micelle size resulting from these polymers varied between 50 and 80 nm (see figure 5). A terminal boronic acid containing group is not detailed nor is the inclusion of the nanoparticles in an anionic polymer containing aqueous medium.
Zhao et al. teach drug delivery micelles composed of amphiphilic block copolymers that include an amphiphilic compound/polymer with a PEG block and oligomethylene block (PEG monostearate) (see abstract). The PEG is provided with a terminal phenylboronic acid as a tumor targeting moiety that is positioned on the surface of the micelle upon self-assembly (see scheme 1 page 14845 second column last partial paragraph-page 14846 first full paragraph). The conjugation of phenylboronic acid occurs at an end of PEG bearing a hydroxyl group (see abstract, scheme 1, page 14846 second column last full paragraph-page 14847 first column first partial paragraph).
Du et al. teach the preparation of block copolymers of PEG and an acrylamide-containing monomer (see abstract.). They employ a similar PEG macroinitiator as Soga et al. except its PEG portions are terminated by hydroxyl functional groups as shown below:
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.
Fan et al. teach that the inclusion of drug releasing nanoparticles in anionic alginate gel that is crosslinked via divalent ions improved the controlled release capabilities of the nanoparticles (see abstract page 2 last paragraph and page 10 last paragraph-page 11 first full paragraph; instant claims 1 and 30). Like the envisioned drugs of Soga et al., their drug is poorly water soluble (see page 2 second full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a variety of the polymer of Soga et al. with a phenylboronic acid terminal on the PEG block. This modification would have been obvious in light of Zhao et al. as the application of the same technique to a similar product in order to yield the same improvement. Du et al. and Zhao et al. demonstrate that the necessary connective chemistry was already known in the art and would have been obvious to apply to facilitate the modification. The inclusion of an envisioned drug in the nanoparticle micelles would follow. In addition, it would have been obvious to include the drug loaded nanoparticle micelles in a crosslinked alginate as detailed by Fan et al. where their drug is encapsuled in the micelles. This modification also would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The recitation of instant claim 45 that states ”formulated for topical administration” is an intended use recitation. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The alginate gel embedded micelle nanoparticles of Soga et al. are capable of being applied topically; thus the intended use limitation is met. Therefore claims 1-3, 6, 8, 10, 13-14, 21, 26-27, 30, and 45 are obvious over Soga et al. in view of Zhao et al., Du et al., and Fan et al.
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.
The following are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 6, 10, 13, 21, 26-27, 30, and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-46 of copending Application No. 18/846446 (reference application) in view of Prosperi-Porta et al. (Biomacromolecules 2016 17:1449−1457) and Zhao et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim an aqueous polymer matrix in which nanoparticle micelles are dispersed. The polymer in both instances is a diblock copolymer of PEG and pHPMA-oligolactate. The micelles encapsulate a hydrophobic therapeutic and is envisioned for topical application to the eye. The presence of a boronic acid terminal moiety of the PEG is not detailed.
Prosperi-Porta et al. teach of a micellar delivery vehicle for h application of drugs to the eye (see abstract. Here the polymer forming the micelles bears phenylboronic acid groups to bind to and target the ocular mucosa (see page 1449 second column first full paragraph-page 1450 first column first partial paragraph and scheme 1).
Zhao et al. teach drug delivery micelles composed of amphiphilic block copolymers that include an amphiphilic compound/polymer with a PEG block and oligomethylene block (PEG monostearate) (see abstract). The PEG is provided with a terminal phenylboronic acid as a targeting moiety that is positioned on the surface of the micelle upon self-assembly (see scheme 1 page 14845 second column last partial paragraph-page 14846 first full paragraph). The conjugation of phenylboronic acid occurs at an end of PEG bearing a hydroxyl group (see abstract, scheme 1, page 14846 second column last full paragraph-page 14847 first column first partial paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a variety of the polymer of the copending claimed with a phenylboronic acid terminal on the PEG block. This choice would have been obvious in light of Prosperi-Porta et al. who detail the benefit of the moiety’s presence and Zhao et al. who show its presence as a terminal group at the end of a PEG block. Therefore claims 1-3, 6, 10, 13, 21, 26-27, 30, and 45 are obvious over claims 27-46 of copending Application No. 18/846446 in view of Prosperi-Porta et al. and Zhao et al.
Claims 1-3, 6, 8, 10, 13-14, 21, 26-27, 30, and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-46 of copending Application No. 18/846446 in view of Prosperi-Porta et al. and Zhao et al. as applied to claims 1-3, 6, 10, 13, 21, 26-27, 30, and 45 above, and further in view of Soga et al.
Claims 27-46 of copending Application No. 18/846446 in view of Prosperi-Porta et al. and Zhao et al. render obvious the limitations of instant claims 1-3, 6, 10, 13, 21, 26-27, 30, and 45. The molecular weight of the two polymer blocks are not detailed.
Soga et al. teach degradable thermosensitive polymer micelles for delivery of drugs (see abstract and page 938 second column and figure 1). The polymer is a diblock copolymer of PEG and poly(hydroxypropylmethacrylamide-oligolactate) According to the instant nomenclature, Y = NH, R3 = alkyl, R2 = substituted alkyl. Soga et al. teach the number average molecular weight of the PEG block as 5000 Da while the pHPMA-DL block is 3000 Da, 6900 Da or 13,600 Da (see page 9389 second column first partial paragraph, and table 1). According to the instant nomenclature, these sizes correspond to n ≈ 24, 48, or 114, respectively.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ polymer block molecular weight as detailed by Soga et al. in the modified product of the copending claims because they were known to be useful for diblock copolymers of PEG and pHPMA-oligolactate employed for micellar drug delivery vehicles. Therefore claims 1-3, 6, 8, 10, 13-14, 21, 26-27, 30, and 45 are obvious over claims 27-46 of copending Application No. 18/846446 in view of Prosperi-Porta et al., Zhao et al., and Soga et al.
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615