DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application was filed 08 December 2022 and is the national stage entry for PCT/IB2021/055116 filed 10 June 2021. The Applicant claims priority to provisional application filed 11 June 2020. Therefore, the effective filing date of the instant application is 11 June 2020.
Examiner’s Note
The Applicant's Pre-Appeal Brief filed 15 July 2026 is acknowledged and has been fully considered. The Examiner has re-weighed all the evidence of record. Rejections not reiterated from previous office actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Prosecution is herein reopened in response to the Pre-Appeal Brief filed 15 July 2026.
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.
Claim(s) 1-5, 9, 10, 13, 18, 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hanes et al. (WO 2017/075565 A1; cited in IDS) in view of Chu et al. (Unambiguous observation of shape effects on cellular fate of nanoparticles, Scientific Reports, 2014), as evidenced by Mutiso (Electrical Conductivity of Polymer Nanocomposites, Polymer Science: A Comprehensive Reference, 2012), dictionary.cambridge.org, and trykepos.com.
Regarding claim 1, Hanes teaches mucus penetrating particles (MPP) (entire teaching, abs) that may comprise anti-cancer agents (pg. 17, ln. 24). The MPPs may be formulated for enteral administration, such as a capsule (pg. 31, lns. 26-28). The composition comprises an active agent incorporated or encapsulated using a coating with a polymer matrix (pg. 8, lns. 17-21). The nanoparticles may be any shape, including spherical and non-spherical shapes (pg. 7, lns. 30-32).
Regarding claims 2 and 4, the coating is interpreted as the outer layer (pg. 8, ln. 24).
Regarding claim 3, the capsules may be in the form of sustained release (pg. 8, ln. 19) and delayed release (pg. 32, ln. 6-14). The capsules may be designed to delay the release of the contents after passing the stomach (pg. 32, lns. 15-16).
Regarding claim 5, the composition comprises anti-cancer drugs (chemotherapy drugs) (pg. 17, lns. 21-30).
Regarding claims 9 and 10, the matrix may comprise PLGA and other biocompatible polymers (pg. 9, lns. 17-32).
Regarding claim 13, the aspect ratio is interpreted as the length over the diameter (evidenced by Mutiso, 7.17.5.1). Since Hanes teaches a particle size of 1-500 nm (pg. 7, lns. 24-28) and that the diameter of a non-spherical particle may be 50-500 nm (pg. 5, lns. 21-23; pg. 7, ln. 32-pg. 8, ln. 1). The length of approximately 250 nm and the diameter of approximately 50 nm is interpreted as falling within the range of 5-100 for the aspect ratio.
Regarding claim 18, the composition comprising surface-modifying agents, such as PEG (pg. 5, lns. 1-7), is interpreted as functionalized with a mucoadhesive agent.
Regarding claim 44, the particle sizes may range from 1 to 500 nm (pg. 7, lns. 24-28) or have a hydrodynamic diameter of 50-500 nm (claim 11).
Hanes does not specifically teach a vertex shape for the particle in claim 1. Hanes does not teach an exact combination of the MPPs with an API and particles shaped with at least one vertex in claim 1.
Chu teaches that nanoparticles with sharp shapes were able to pierce membranes and were essential for drug delivery (abs). Chu specifies that nanoparticles with “sharp corner and edges” could easily penetrate the endosomal membranes (pg. 1). Chu also provides examples of nanostars, which have a high sharpness compared to nanospheres (see Figure 6), penetrating at a cellular level (pgs. 6-7).
In regards to selecting the combination of MPPs, PLGA, anticancer agents, and capsule in at least claim 1, “[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)). “When 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 obvious to have selected various
combinations of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Hanes et al. teach mucus penetrating particles (MPP) (entire teaching, abs) that may comprise anti-cancer agents (pg. 17, ln. 24), whereas the claimed invention is directed towards a drug delivery device comprising an enteric capsule, API, matrix, wherein the particles have at least one vertex. Since Hanes teaches the individual components of the claimed composition, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients to arrive at the claimed invention with a reasonable expectation of success.
Since Hanes does not specifically teach a vertex shape for the particle in claim 1, one of ordinary skill in the art would have been motivated to use Chu’s teaching of sharp or star-shaped nanoparticles with a reasonable expectation of success. Absent of a clear definition of “vertex” provided by the Applicant, the term “vertex” is defined and interpreted as a point where two lines meet to form an angle (evidenced by dictionary.cambridge.org, pg. 1). Therefore, Chu’s teaching of nanoparticles with sharp corners and edges, as well as nanostars, reads on the limitation of vertex. Furthermore, Chu’s nanostars and sharp nanoparticles that are capable of penetrating the membranes of cells are interpreted as capable of penetrating the lining of a gastrointestinal tract by piercing the lining and embedding in the lining, as the gastrointestinal tract lining is also considered a single cellular level barrier (evidenced by trykepos.com, pg. 1).
Additionally, a person of ordinary skill in the art would have been led to combine the teachings because Hanes teaches mucus penetrating particles with any spherical or non-spherical shape and Chu specifies that nanoparticles with vertices or sharp features are better for drug delivery. “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 MPEP § 2144.07).”
Claim(s) 15-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hanes et al. (WO 2017/075565 A1; cited in IDS) in view of Chu et al. (Unambiguous observation of shape effects on cellular fate of nanoparticles, Scientific Reports, 2014), as applied to claim(s) 1-5, 9, 10, 13, 18, 44 above, and further in view of Gentile et al. (An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering, Int. J. Mol. Sci., 2014), Demir et al. (Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery, PLoS One, 2013), and Arora et al. (Micro-scale Devices for Transdermal Drug Delivery, Int J Pharm, 2008), as evidenced by Mutiso (Electrical Conductivity of Polymer Nanocomposites, Polymer Science: A Comprehensive Reference, 2012), dictionary.cambridge.org, and trykepos.com.
In regards to claim(s) 1-5, 9, 10, 13, 18, 44, Hanes et al., as applied supra, is herein applied in its entirety for its teachings of mucus penetrating particles (MPP) comprising anti-cancer agents.
Hanes does not specifically teach values for the elastic modulus, axial failure, and sharpness in claims 15-17.
In regards to claims 15-17, the elastic modulus, axial failure, and sharpness can vary depending on the components of the product and the intended use. However, Gentile teaches that PLGA used in drug delivery may be around 2.0 GPa (Table 1), Demir teaches that PLGA may have an axial failure force of around 1 N (Table 2) in their drug delivery system, and Arora teaches that sharpness in drug delivery products designed to penetrate skin or tissue may be around 1-25 um (pg. 7, para. 4). Furthermore, “products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. “The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.”). Additionally, 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.
In regards to claims 15-17, the ranges for elastic modulus, axial failure force, and sharpness can be viewed as a variable that achieves the recognized result of successfully making the drug particle composition. The optimum or workable range for the elastic modulus, axial failure force, and sharpness can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized ranges of elastic modulus, axial failure force, and sharpness as nonobvious.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hanes et al. (WO 2017/075565 A1; cited in IDS) in view of Chu et al. (Unambiguous observation of shape effects on cellular fate of nanoparticles, Scientific Reports, 2014), Gentile et al. (An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering, Int. J. Mol. Sci., 2014), Demir et al. (Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery, PLoS One, 2013), Arora et al. (Micro-scale Devices for Transdermal Drug Delivery, Int J Pharm, 2008), as applied to claim(s) 1-5, 9-10, 13, 15-18, 44, and further in view of Haggag et al. (Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice, Biomedicine & Pharmacotherapy, 2018), as evidenced by Mutiso (Electrical Conductivity of Polymer Nanocomposites, Polymer Science: A Comprehensive Reference, 2012), dictionary.cambridge.org, and trykepos.com.
In regards to claim(s) 1-5, 9, 10, 13, 15-18, 44, Hanes et al., as applied supra, is herein applied in its entirety for its teachings of mucus penetrating particles (MPP) that may comprise anti-cancer agents.
Hanes does not teach a specific anti-cancer agent in claim 6.
Haggag et al. teach that encapsulation of 5-fluorouracil in PLGA nanoparticles enhanced the anti-cancer activity of the drug and improved sustained release (entire teaching, abs).
Since Hanes does not teach a specific anti-cancer agent but does teach using anti-cancer agents in their nanoparticle drug delivery system in claim 6, one of ordinary skill in the art would have been motivated to use Haggag’s teaching of encapsulating 5-fluorouracil (interpreted as a small molecules) in PLGA nanoparticles with a reasonable expectation of success. A person of ordinary skill in the art would have been reasonably motivated to use these teachings because Haggag’s composition shows improved sustained release and enhanced anti-cancer activity when encapsulated in a nanoparticle system for oral delivery (pg. 215, right column). “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 MPEP § 2144.07).”
Response to Arguments
Applicant's Pre-Appeal Brief filed 15 July 2026 have been fully considered but they are not persuasive.
The Applicant argues that the Office Action fails to show that Chu’s sharp shaped nanoparticles are capable of penetrating a lining of a gastrointestinal tract (Brief, pgs. 2-3). The Applicant further argues that the scale at which Chu’s nanoparticles penetrate is different from the claimed invention (Brief, pg. 3).
Applicant’s argument is not found persuasive. Chu teaches that nanoparticles with sharp shapes were able to pierce membranes and were essential for drug delivery (abs). Chu specifies that nanoparticles with “sharp corner and edges” could easily penetrate the endosomal membranes (pg. 1). Chu also provides examples of nanostars, which have a high sharpness compared to nanospheres (see Figure 6), penetrating at a cellular level (pgs. 6-7).
Since Hanes does not specifically teach a vertex shape for the particle in claim 1, one of ordinary skill in the art would have been motivated to use Chu’s teaching of sharp or star-shaped nanoparticles with a reasonable expectation of success. Absent of a clear definition of “vertex” provided by the Applicant, the term “vertex” is defined and interpreted as a point where two lines meet to form an angle (evidenced by dictionary.cambridge.org, pg. 1). Therefore, Chu’s teaching of nanoparticles with sharp corners and edges, as well as nanostars, reads on the limitation of vertex. Furthermore, Chu’s nanostars and sharp nanoparticles that are capable of penetrating the membranes of cells are interpreted as capable of penetrating the lining of a gastrointestinal tract by piercing the lining and embedding in the lining, as the gastrointestinal tract lining is also considered a single cellular level barrier (evidenced by trykepos.com, pg. 1).
Additionally, a person of ordinary skill in the art would have been led to combine the teachings because Hanes teaches mucus penetrating particles with any spherical or non-spherical shape and Chu specifies that nanoparticles with vertices or sharp features are better for drug delivery. “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 MPEP § 2144.07).”
The Applicant argues that the Office Action fails to show that a skilled artisan would have been motivated to modify the particles of Hanes based on the teachings of Chu (Brief, pgs. 3-4). The Applicant further argues that Hanes’ MPPs are designed to diffuse through mucus barriers (Brief, pg. 3).
Applicant’s argument is not found persuasive. Chu teaches that their nanoparticles with sharp corners, shapes, and edges were able to pierce membranes and were essential for improved drug delivery (abs). Therefore, a person of ordinary skill in the art would have been led to combine the teachings of Hanes and Chu with a reasonable expectation of success to improve Hanes’ drug delivery composition. Hanes teaches MPPs with any spherical or non-spherical shape for delivering anti-cancer agents and Chu specifies that nanoparticles with vertices or sharp corners and edges can pierce membranes and enhance drug delivery. Assuming arguendo that Hanes’ MPPs are designed purely to diffuse the mucus barrier, the ability of the nanoparticles to penetrate the lining and enhance drug delivery from Chu’s teaching would likely improve the absorption and delivery of drugs in Hanes’ teaching.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danielle Kim whose telephone number is (571)272-2035. The examiner can normally be reached M-F: 9-5 p.m. PST.
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/D.A.K./Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613
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