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 .
Status
Claims 1-4, 6, 10-14 and 16-26 are pending.
Rejections not reiterated in this action are withdrawn.
Priority
This application is a CON of PCT/CN2021/102758 (06/28/2021),
and claims foreign priority to CHINA 202010611437.4 (06/30/2020),
and CHINA 202011633559.X (12/31/2020).
New 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 1-3, 6, 10-11, 20, 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US10696985) in view of Deirram et al. (“pH-Responsive Polymer Nanoparticles for Drug Delivery,” Macromol. Rapid Commun. 2019, 40, 1800917, 23 pages).
Regarding amended claim 1, Wilson teaches in Fig. 1:
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And defines a scope where z=0, which corresponds to the same polymer structure of claim 1, Formula (I), where claim 1’s
x, n, m corresponds to Wilson’s m, x, y (z=0);
R1 corresponds to Wilson’s -CH2-CH2-N-(Et)2;
R2 corresponds to Wilson’s -n-butyl.
Wilson teaches the polymer is pH responsive (Figs. 3, 11, col 2, lines 62-65) which can be “precisely tuned” (col 10, lines 9-28: “the pH responsive behavior can be precisely tuned through control of monomer composition”; col 12, lines 5-39). Wilson teaches a scope of amine-containing monomers for the hydrophilic group as including -CH2-CH2-N-(Et)2 and N-morpholinoethyl (claim 9; col 8, lines 23-37). Wilson teaches y is in the range of 30-60%, and in an embodiment is 35% (corresponding to claim 1’s “m is 15%-40% of n+m”) (col 9, lines 30-56, claim 13-15). Wilson teaches modification of polymer components/sidechains to optimize therapeutic effect (Wilson cols 5-6, claims 32-43, Title: “polymer vesicles for cytosolic drug delivery”).
Although Wilson teaches the polymer with a diethylamino (-N-(Et)2) and N-morpholinoethyl, Wilson does not teach a piperidinyl as the sidechain.
Deirram reviews drug delivery of therapeutics using pH-responsive polymer nanoparticles (Title, Abstract), including how the pH sensitivity can be successfully tuned in vivo via altering the sidechain of the polymer from diethylamino to piperidinyl (Fig 4, PDEA, PC6A, PC7A):
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Deirram teaches the two most successful screened polymer variants where PC6A and PC7A as shown above which were significantly improved over PDEA (diethylamino sidechain) (Fig. 1B).
One of ordinary skill in the art following the teaching of Wilson would have considered known techniques for tuning the pH sensitivity of the polymer to optimize therapeutic effect and considered the teaching of Deirram showing success in changing diethylamino (-N-(Et)2, as taught by Wilson; Deirram’s PDEA) to piperidinyl (Deirram’s PC6A) with a reasonable expectation of success, particularly in view of Deirram’s in vivo experiments with a chemically related polymer. Thus, at least claims 1-3, 6, and 10 are obvious.
Regarding claim 11, Wilson does not teach azepanyl as the sidechain. As with claim 10, Deirram reviews drug delivery of therapeutics using pH-responsive polymer nanoparticles (Title, Abstract), including how the pH sensitivity can be successfully tuned in vivo via altering the sidechain of the polymer from diethylamino to azepanyl (Fig 4, PDEA, PC6A, PC7A). One of ordinary skill in the art following the teaching of Wilson would have considered known techniques for tuning the pH sensitivity of the polymer to optimize therapeutic effect and considered the teaching of Deirram showing success in changing diethylamino (-N-(Et)2, as taught by Wilson; Deirram’s PDEA) to azepanyl (Deirram’s PC7A) with a reasonable expectation of success, particularly in view of Deirram’s in vivo experiments with a chemically related polymer.
Regarding claim 20, Wilson teaches a polymer vesicle formed in aqueous media via self-assembly (claim 18; Fig. 2; col 2, lines 41-42).
Regarding claim 23-24, Wilson teaches the vesicles used in a method of releasing an active agent to a cancer cell (claim 43) and treating tumors (Fig 13, col 5), including melanoma (col 5, lines 34-40).
Claims 4, 12-14, 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US10696985) in view of Deirram et al. (“pH-Responsive Polymer Nanoparticles for Drug Delivery,” Macromol. Rapid Commun. 2019, 40, 1800917, 23 pages) as applied to claims 1-3, 6, 10-11, 20, 23-24 above and further in view of Huo et al. (“Controlling Vesicular Size via Topological Engineering of Amphiphilic Polymer in Polymerization-Induced Self-Assembly,” Macromolecules 2017, 50, 9750−9759).
Regarding claim 4, Wilson teaches an aromatic pendant group (col 8, lines 37-45; claim), but does not specifically teach benzyl.
Regarding claim 12, although Wilson teaches the polymer is self-assembling (col 2, line 41-42) including blocks with sidechains that facilitate self-assembly (col 7, lines 50-62; col 9, lines 57-62; claim 17), Wilson does not teach a benzyl polymer sidechain.
Hou teaches preparation of polymer vesicle nanoparticles useful for pharmaceutical application and tuning vesicle size by altering the ratio of polymer monomers, including benzyl methacrylate (BzMA) (Title, Abstract, p. 9750) in a related polymer system (Hou Scheme 1):
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.
One of ordinary skill in the art following the teaching of Wilson for drug delivery vesicles would have considered Hou’s teaching of tuning the vesicle nanoparticle size by including BzMA and altering the ratios to achieve an optimal size for drug delivery therapeutic effect. Such optimizations are well within the technical grasp of one of ordinary skill in the art and implementing changes in monomers used in polymerization would be considered routine. In addition, one of ordinary skill in the art would have had a reasonable expectation of success due to the same field of endeavor and the structural similarities among the polymer systems.
Regarding claims 13-14, 16-19, each of Wilson, Deirram, and Hou teach tuning the properties of the nanoparticles through altering the ratios of monomers in the polymerization. Application of the same technique is routine in the art and one of ordinary skill in the art would arrive at the claimed ranges through routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); MPEP 2144.05. In this case, the prior art establishes that the ratio of polymer monomers is a results effective variable that controls the properties of the resulting nanoparticles formed therefrom.
Claims 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US10696985) in view of Deirram et al. (“pH-Responsive Polymer Nanoparticles for Drug Delivery,” Macromol. Rapid Commun. 2019, 40, 1800917, 23 pages) as applied to claims 1-3, 6, 10-11, 20, 23-24 above and further in view of Li et al. (“Smart Superstructures with Ultrahigh pH Sensitivity for Targeting Acidic Tumor Microenvironment: Instantaneous Size Switching and Improved Tumor Penetration,” ACS Nano 2016, 10, 6753−6761).
Wilson teaches the polymer material according to claim 1 as detailed in the 35 USC 103 rejections supra and incorporated herein.
Regarding claim 21 to a preparation method with steps of dissolving the polymer material in solvent, DMF, adding to water in drops under stirring, and removing the solvent through dialysis, Wilson teaches dissolution in a water miscible organic solvent, dropwise addition to aqueous medium, vortexing, and dialysis (col 13, lines 21-62; col 12, lines 58-61).
Wilson does not specifically teach the use of DMF.
Li teaches preparation of related polymer nanoparticles through the use of DMF and dialysis in the preparation of structurally similar polymer nanoparticles in the same field of endeavor (p. 6759: “Experiment Section”). One of ordinary skill in the art would have considered using DMF as it is water miscible and was successfully used by Li in a related application.
Regarding claim 22, the prior art does not teach the specific ratio of solvent, stirring speed, time, or molecular cutoff for dialysis, but instead teaches the general conditions which one of ordinary skill in the art would need to select from and using their high level of experience in the art would arrive at the claimed values in the course of routine experimentation. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); MPEP 2144.05.
Claims 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US10696985) in view of Deirram et al. (“pH-Responsive Polymer Nanoparticles for Drug Delivery,” Macromol. Rapid Commun. 2019, 40, 1800917, 23 pages) as applied to claims 1-3, 6, 10-11, 20, 23-24 above and further in view of Chen et al. (“Antibacterial polymeric nanostructures for biomedical applications,” Chem. Commun., 2014, 50, 14482-14493).
Wilson teaches the polymer material according to claim 1 as detailed in the 35 USC 103 rejections supra and incorporated herein. Wilson further teaches that the polymer vesicles include active agents including antibiotics (col 10, lines 29-43).
Regarding claim 24, Wilson teaches the drug of claim 23 but does not teach formulation for bacterial infection.
Chen teaches antibacterial polymeric nanoparticles comprising structurally similar polymers (Abstract, Figs. 1-6) applied to bacteria including E. coli and S.aureus (p. 1484-86). One of ordinary skill in the art following the teaching of Wilson would have considered applying the polymer vesicles as an antibacterial as specifically suggested by Wilson and detailed by Chen. One of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention because the prior art are in the same field of endeavor and because of the structural similarities among the polymers.
With each of the above claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art in the same field of endeavor. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant amended the claims and argues that Wilson does not teach R4 and R5 together form a piperidinyl or azepinyl and Deirram, Huo, Li and Chen cannot cure the deficiencies of Wilson. This argument is not persuasive as detailed in the rejections above, Wilson does teach generically a hydrophilic amine monomer group that is pH responsive amine-containing including -CH2-CH2-N-(Et)2 and N-morpholinoethyl which are structurally similar to the compounds that Deirram optimizes and tests experimentally to find both piperizinyl and azepinyl as having the greatest efficacy. Thus, the prior art suggested the claimed invention to one of ordinary skill in the art with a reasonable expectation of success.
Applicant argues that the results in the specification show that the claimed invention has optimal tumor cell killing activity at the desired pH conditions. This argument is not persuasive as this is the same suggestion and optimization that was performed in the prior art and led to the same results. Thus, one of ordinary skill in the art would have arrived at the claimed invention in the same manner.
Applicant argues that Wilson and the secondary references do not disclose that the polymer material itself has anti-tumor or antibacterial effects. The argument is not persuasive because the instant claims are to a product that is rendered obvious regardless of the intended use.
Applicant argues that the polymers of the cited are all completely different from the structure of the polymer as claimed. This is not persuasive as Wilson is substantially identical to the instant claims, but for the hydrophobic amine group (prior to the claim amendment were anticipated by Wilson). Furthermore, the cited secondary references are also of a similar polymer structure with repeating group having the same function such that one of ordinary skill in the art would combine the teachings of them.
Conclusion
No claims allowed.
Any new grounds of rejection in this action were necessitated by Applicant's amendment. 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.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626