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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 21 October 2025 has been entered.
Status of the Claims
Claims 1, 2, 5, 9-16, 18, 21-23, and 26 are pending.
Claims 9, 18, 21-23, and 26 are withdrawn from consideration as directed to non-elected inventions.
Claims 1, 2, 5, and 10-16 are presented for examination and rejected, as set forth below.
Claim Interpretation
Applicants claims are directed to compositions combining a core-corona structure, more commonly referred to as a “core-shell” structure, of defined particle size and polydispersity comprising a copolymer having a hydrophilic block which is a hydrolyzed galactomannan and a hydrophobic block that contains a poly(methyl)methacrylate, where the hydrophobic portions contain monomeric units selected from Markush-type listings of alternatives, where the hydrophobic portion of the amphiphile is present in a defined concentration range and the copolymer possesses a molecular weight within a defined range. Claims 2 and 5 further narrow the identity of the polysaccharide to galactomannan, indicating that at least a portion of the hydrophilic domain possess affinity for the GLUT family of receptors. The examiner notes that the art supports the conclusion that galactomannan polymers inherently possess these properties. See, e.g., Mike Mueckler & Bernard Thorens, The SLC2 (GLUT) Family of Membrane Transporters, 34 Mol. Asp. Med. 121, 123 (2013) (establishing that each of galactose and mannose are substrates for a variety of GLUT transport proteins). Claim 10 indicates that the composition copolymer is biodegradable. Claim 11 defines the HLB of the copolymer. Claims 12-15 indicate that an active agent is to be encapsulated within or attached to the hydrophobic portion of the copolymer, to remain stably incorporated for a defined period of time, and narrow the identity of the agent so incorporated. Claim 16 indicates that at least a portion of the copolymer is charged.
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 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, 2, 5, and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Sosnik (WO2017/002114) as evidenced by Mueckler (Mike Mueckler & Bernard Thorens, The SLC2 (GLUT) Family of Membrane Transporters, 34 Mol. Asp. Med. 121, 123 (2013)), in view of Moretton (Marcela A. Moretton, et al, Hydrolyzed Galactomannan-Modified Nanoparticles and Flower-Like Polymeric Micelles for the Active Targeting of Rifampicin to Macrophages, 9 J Biomed. Nanotech. 1 (2013)).
Sosnik describes compositions comprising amphiphilic block copolymers configured to provide a hydrophobic core and hydrophilic corona to encapsulate hydrophobic therapeutic agents, addressing limitations of Claims 1, 12, and 15. (Abs., Pg. 2; 30). Representative hydrophobic domains of the amphiphilic block copolymer include polymers of the (methyl)methacrylate of Claim 1. (Pg. 2-3). Representative hydrophilic corona blocks of the amphiphilic copolymer include polymers derived from galactomannan of Claim 1 which applicants have elected, addressing the limitations of Claims 2 and 5 as well. (Pg. 3), see also Mueckler pg.123 “Table 1” (indicating that each of galactose and mannose are substrates for a variety of GLUT transport proteins). Sosnik indicates that these hydrophilic backbone should possess an average molecular weight of between 1000-10,000,000 g/mol, or can be present in copolymers in weights as low as 500 g/mol, a range overlapping and therefore rendering obvious those of the instant claims. (Pg. 12), 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.”). In addition, Sosnik indicates that the hydrophobic blocks present in the amphiphilic copolymers should be present in masses of between 100-10,00 g/mol, or between 200-5,000 g/mol, which are to be grafted onto the hydrophilic polymer portion of the amphiphile. (Pg.13-15). Taken in combination, then, Sosnik suggests amphiphilic copolymers having molecular weights as low as 1100 g/mol, a value falling within and therefore rendering obvious the language of Claim 1 concerning the overall weight of the amphiphilic copolymer. Sosnik teaches that embodiments of their invention employ hydrophilic copolymers which are non-crosslinked, addressing limitations of Claim 3. (Pg.11). Sosnik describes embodiments of these amphiphilic block copolymers as possessing the hydrophobic domain as present in between 10-90% of the weight of the amphiphilic block copolymer overlapping and therefore addressing the limitation newly added to Claim 1, as being biodegradable thereby addressing the limitations of Claim 10, and of possessing an HLB balance of between 1-24 addressing the limitations of Claim 11. (Pg. 3). Sosnik describes these compositions as stably encapsulating within the core active agents for a period of time of at least 24 hours, addressing the limitations of Claim 13. (Pg. 4). Sosnik indicates that at least a portion of the hydrophilic corona is non-covalently linked to a charged moiety, implying that the corona itself is charged in a manner to accommodate the non-covalent linkage of the charged material so associated, addressing the limitations of Claim 16. (Id., Pg. 21-22). Sosnik describes these core-corona structures as possessing sizes falling within the range of 10nm to 10 microns, a range overlapping and therefore rendering obvious that of instant Claim 1. (Pg. 21). 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.”). The examiner additionally notes that while no explicit requirement on the polydispersity of these particles is required, Sosnik exemplifies a preference for uniformity of samples to contribute to more defined biodistribution, and explains that a PDI between 0.01-0.1 is preferable, this range being less than 0.4 as is required by the claims, rendering such a property the predictable use of prior art elements according to their established functions and obvious thereby. See pg.23, pg.52 “Table 7”; pg.53 “table 8”; pg.54 “Table 9”; pg.60 “Table 14”; see also KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007). Sosnik describes the agents for incorporation into the core of the amphiphilic core-corona structure as including the anticancer drugs applicants have elected as representative of the agents of instant Claim 14. (Pg. 27-28; 30).
The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any motivation to select this specific combination of amphiphilic copolymer containing between 10-90% hydrophobic acrylate and galactomannan having a molecular weight of about 1000g/mol forming the at least partially charged hydrophilic corona to stably encapsulate for at least 24 hours within a biodegradable 10nm-10micron micelle having a PDI of less than 0.4 containing a hydrophobic anticancer agent, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have assembled an amphiphilic copolymer by grafting between 10-90% hydrophobic (methyl)methacrylate onto a galactomannan backbone to provide an amphiphilic copolymer having a molecular weight of about 1100g/mol forming an at least partially charged non-crosslinked hydrophilic corona to stably encapsulate for at least 24 hours within a biodegradable 10nm-10micron micelle having a PDI of less than 0.4 containing a hydrophobic anticancer agent from within the Sosnik disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Despite the breadth of the Sosnik and Mueckler disclosures relevant to the present claims, neither reference suggests that the hydrophilic polymer be a hydrolyzed galactomannan. However, Sosnik does teach that the hydrophilic polymers useful in the compositions disclosed may be modified natural polymers. See Sosnik pg.11, L.32-34.
This is cured by the teachings of Moretton which establishes that in the context of drug delivery, subjecting galactomannans to acid hydrolysis employing trifluoroacetic acid usefully improves hydrophilicity by imparting greater water solubility, lower viscosity, and controls the molecular weight range to 3500 g/mol or less. (pg.2-3)
On the basis of the fact that the art teaches that hydrolysis of galactomannans improves aqueous solubility of polysaccharides useful in drug delivery applications while reducing molecular weight to a range overlapping that required by Sosnik, the skilled artisan would have found it obvious to have selected a hydrolyzed galactomannan as the modified natural polysaccharide Sosnik teaches is a useful hydrophilic component of the core-corona structures described as useful drug delivery constructs. This is because generally it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (indicating that "Reading a list and selecting a known component to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle. It is not invention.”).
Response to Arguments
Applicant's arguments filed 21 October 2025 have been fully considered.
Applicants assertion that the art of record fails to teach each limitation of the claims is inaccurate, as set forth in greater detail above.
Applicants assertion that the difference in CMC between those of the prior art Sosnik reference and those of the instant claims presents sufficient evidence of secondary indicia of nonobviousness are unpersuasive. This is because the PMMA particles of Sosnik address the limitations of the present claims, and nothing of record in the present application provides evidence tending to establish that whatever minor difference in CMC may be demonstrated by the exemplary polymers of the prior art compared to those of the instant claims is of statistical or practical significance. “[A]ppellants have the burden of explaining the data…they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). The evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).
Applicants reiteration of arguments presented previously and of the data presented and discussed by inventor declarant Sosnik remain unpersuasive for the reasons set forth previously. More specifically, applicants are reminded that the Sosnik reference of record describes multiple nanoparticles of particle size between 20-400nm having a polydispersity of less than 0.4, overlapping and therefore addressing what is required by the claims. See, e.g., Sosnik Examples 7 and 8 (Pg.52-53), 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.”). While some difference in particle sizes and CMCs may be observed when comparing the Sosnik prior art polymer micelles with those of the instant claims, Applicants are reminded that any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, the record cannot support that conclusion. Indeed, the data presented by inventor declarant Sosnik concludes that it is the control of the relative amount of PMMA in the polymer that results in the obtention of particles having the desired size and polydispersity. See Declaration sections 5-6. The skilled artisan would, of course recognize this as the inventor declarant asserting that, in the context of a PMMA/galactomannan copolymer, the hydrophilic/ lipophilic balance of the polymer contributes to the control of resultant encapsulating particle size and polydispersity. See Sosnik pg. 45; instant Specification [0349]. This is entirely expected given the understanding of a person having ordinary skill in the art. See Mattia Sponchioni, et al, Influence of the Polymer Structure Over Self-Assembly and Thermo-Responsive Properties: The Case of PEG-b-PCL Grafted Copolymers via a Combination of RAFT and ROP, 54 J Polym. Sci. Part A: Polym. Chem. 2919 (2016)(of record) (monodisperse nanoparticles obtained from hydrophilic/hydrophobic block copolymers, with the size of the particles related to the relative length of the copolymer blocks). “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967), see also In re Skoner, 517 F.2d 947, 950 (CCPA 1975).
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614