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 .
This action is in response to the amendment, filed 8/25/2025, in which claims 20, 23, 24 and 27-29 were canceled, and claims 19, 21, 22, 25, 26 and 32 were amended. Claims 1-19, 21, 22, 25, 26 and 30-32 are pending.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the reasons that follow. Any rejections and objections not reiterated in this action have been withdrawn. This action is FINAL.
Election/Restrictions
Applicant elected Group II (claims 19-32) drawn to uniform polyelectrolyte complex (PEC) nanoparticle(s) without traverse. Applicant elected polyethylenimine (PEI) as the polycationic polymer; nucleic acid as the polyanionic polymer, and plasmid DNA as the nucleic acid; and cytokine as the therapeutic agent.
Claims 1-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The elections were made without traverse.
Claims 19, 21, 22, 25, 26 and 30-32 are under consideration.
Drawings
The drawings were received on 8/25/2025. These drawings are acceptable.
Specification
The substitute specification filed 8/25/2025 has been entered.
Response to Arguments - Claim Objections
The objection to claim 27 is moot in view of Applicant’s cancellation of the claim in the reply filed 8/25/2025. It is noted that linear polyethylenimine has been spelled out at the first occurrence of the abbreviation in claim 19.
Response to Arguments - 35 USC § 112
The rejection of claims 25, 26 and 32 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn in view of Applicant’s amendment to the claims in the reply filed 8/25/2025.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 19, 21, 25, 26 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent 2017/042829A1 (Mao et al. Cite No. 3 on IDS filed 09/13/2023). This rejection was made in the Office action mailed 2/25/2025 and has been rewritten to address the amendment to the claims in the reply filed 8/25/2025.
With regard to claim 19, Mao et al. discloses subject matter providing a flash nanocomplexation (FNC) method which creates a continuous generation of uniform polyelectrolyte complex (PEC) nanoparticles. (See pp. 2; [0011]).
With regard to the product by process limitations of instant claim 19, MPEP §2113(I) states: “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” (In re Thorpe, 227 USPQ 964,966). Once the Examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product (In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983), MPEP 2113).
Mao et al. discloses that “In various embodiments, polyelectrolyte complexes are formed when macromolecules of opposite charge are allowed to interact. For example, in some embodiments, flash precipitated nanoparticles of polyelectrolyte complexes are formed by rapidly and homogenously mixing streams, i.e., a water-soluble polycation dissolved in a stream and a water-soluble polyanion dissolved in a stream.” (See pp. 5; [0060].)
With regard to the structural limitations provided by claim 19, it is noted that each required value is preceded by the term “about,” which is defined as referring to values including ±100%. See the paragraph bridging pp. 26-27.
Mao et al exemplify the production of nanoparticles by FNC at a flow rate of 20 mL/min using 25 μg/mL plasmid DNA and a pH value of 3.5 for lPEI solution (See pp. 12; [0127]). Mao et al teach that the produced nanoparticles have an average of 4.2 plasmid DNA molecules per nanoparticle (See pp. 12; [0127]). Mao et al teach that at a pH of 4.5, there is a transition in shape of nanoparticles to a rod shape, whereas at lower pH, the nanoparticles are very uniform and spherical with a diameter of 30-40 nm (See pp. 12; [0126]).
The Examiner notes that Mao et al. does not disclose the percentage of bound lPEI to total LPEI. The claim requires between about 50% to about 75%. The instant disclosure teaches that “the overall conclusion is clear that the binding of lPEI to pDNA to form PEC is not affected by the concentrations of either pDNA or lPEI, nor by the input N/P ratio.” See the paragraph bridging pp. 34-35. In all situations tested in the instant disclosure, “the amount of bound lPEI was nearly all around 70%.” See the paragraph bridging pp. 34-35.
Mao et al. discloses the polydispersity index (PDI) of the generated polyelectrolyte complex nanoparticles may range from about 0.05 to about 0.2 (substantially identical to claimed range; with sufficient specificity) (See pp.8; [0092])
Mao et al. discloses that uniform PEC nanoparticles are generated by flash nanocomplexation (FNC) (See pp. 2; [0012]). Additionally, Mao et al. discloses that nanoparticles prepared by FNC have an average positive surface charge of +30mV in water (See pp.12; [0128] and Fig. 12B. Also, see instant application specification pp. 23, 24, and 37, lines 29-31, lines 1-10, and lines 23 and 24, respectively; the “PDI ranges from 0.05 to 0.2”, a “plurality of PEC nanoparticles has a PDI between 0.1 and about 0.25”, the PEC nanoparticle “surface charge is between +20 to about 50+ mV”, the “hydrodynamic density is between 60 Da/nm3 to about 80 Da/nm3”, “the PEC nanoparticle has an apparent hydrodynamic density of about 67.68 Da/nm3”, and “more specifically, these nanoparticles have the same apparent hydrodynamic density of 67.68 Da/nm3”).
The Examiner notes that Mao et al. does not disclose the percentage of bound lPEI to total PEI or the hydrodynamic density properties as recited in claim 19. However, the invention as claimed is not structurally distinguishable from the disclosure of Mao et al. The same process is used to produce the same nanoparticles. Therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “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.
With regard to claim 21, Mao et al. teach the nanoparticle has an average of 4.2 copies of plasmid DNA per nanoparticle (See pp. 12; [0128]), which is about 4.4 copies of plasmid DNA per nanoparticle.
With regard to claims 25 and 26, Mao et al. discloses an N/P of 8 for lPEI-DNA complex (See pp. 8; [0032] and pp. 10; [0115]).
With regard to claim 30, Mao et al. discloses that the FNC process can be applied for preparing DNA and RNA containing nanoparticles with other polycationic carriers (See pp. 12-13; [0132]).
Response to Arguments - 35 USC § 102
The rejection of claims 20, 23, 24 and 27-29 under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent 2017/042829A1 (Mao et al.) is moot in view of Applicant’s cancellation of the claims in the reply filed 8/25/2025.
With respect to the rejection of claims 19, 21, 25, 26 and 30 under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent 2017/042829A1 (Mao et al.), Applicant's arguments filed 8/25/2025 have been fully considered but they are not persuasive.
The response asserts that the prior Office action on page 11 acknowledged that Mao does not disclose the hydrodynamic density properties recited in claim 29. Thus, the response asserts that Mao does not anticipate the claims, because a claim is anticipated only if each and every element as set forth in the claim is found, either expressly or inherently described in a single prior art reference.
This argument is not found persuasive. The claimed hydrodynamic properties are not expressly taught by Mao et al. However, the rejection of record provides a rationale to support the shared inherent features of Mao et al. and the claimed nanoparticles. Both the instant claims and the prior art teach the same FNC process of producing nanoparticles from plasmid DNA and lPEI. Thus, the properties should also be the same. The response does not prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product.
Thus, the rejection is maintained.
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.
Claims 22 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Mao et al. as applied to claims 19, 21, 25, 26 and 30 above, and further in view of Bordelon et al. (“Characterization of plasmid DNA location within chitosan/PLGA/pDNA nanoparticle complexes designed for gene delivery.” Journal of Nanomaterials 2011 (2011): 8). This rejection was made in the Office action mailed 2/25/2025 and has been rewritten to address the amendment to the claims in the reply filed 8/25/2025.
Applicant Claims
The instant application claims the following:
Claim 22: The PEC nanoparticle of claim 19, wherein the PEC nanoparticle has one pDNA per nanoparticle.
Claim 31: The pharmaceutical formulation of claim 30, wherein the formulation comprises a lyophilized formulation.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Mao et al. is directed to a method, flash nanocomplexation (FNC), for continuous generation of uniform polyelectrolyte complexes (PEC) to optimize the assembly of nanoparticles. (See pp.1; [0009]). Moreover, Mao et al. teaches that the average number of DNA per nanoparticle was found to be 4.2 with fast mixing and 4.7 with bulk mixing. (See pp. 4; [0039]).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Mao et al. does not teach one copy of plasmid DNA per nanoparticle, as required by instant claim 22. Mao et al. also does not teach a lyophilized formulation as required by instant claim 31. However, this deficiency is cured by Bordelon et al.
Bordelon et al. is directed to a polyelectrolyte complex, Poly (D, L-lactide-co-glycolide) (PLGA-) chitosan nanoparticles, as a common complex to deliver nucleic acids to cells for genetic manipulation techniques (See pp. 1, Abstract). Additionally, Bordelon et al. is directed to determine the optimal ratio of plasmid DNA (pDNA) to nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within the complexes (See pp.1, Abstract). Bordelon and colleagues teach 1:1 pDNA/NP complex. (See pp. 3, under “3.4 Chi/PLGA-pDNA Complex Formation” and pp. 5, Figure 4(a) gel electrophoresis).
Bordelon and colleagues also disclose that the PLGA (Poly (DL-lactide-co-glycolide)) nanoparticle synthesis involves freeze drying (otherwise known as lyophilization) (See pp. 2; Methods Section 3.1 PLGA Nanoparticle Synthesis). Bordelon et al. teach that variations in chitosan type and content, PLGA type, and particle preparation methods (i.e., centrifugation, freeze-drying) have been used to change NP characteristics such as article size and overall surface charge and have been shown to directly affect the binding efficiencies of the particles to nucleic acids such as antisense DNA oligonucleotides [24, 25] and small interfering RNAs [26] (Introduction section).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Mao et al. and Bordelon et al. are both directed to the optimization of the PEC nanoparticles/nucleic acid complex. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was filed, to modify the 4:2 and 4:7 nucleic acid to nanoparticle ratios of Mao et al. with the 1:1 pDNA to nanoparticle ratio to achieve the predictable result of obtaining a composition suitable for creating uniform PEC/nanoparticle complexes. One of ordinary skill in the art would have been motivated to do so because Bordelon et al. teach a 1:1 ratio of pDNA/NP complex and that an inconsistent ratio of pDNA to nanoparticles cause variations of pDNA coverage of the nanoparticle complexes (See pp. 7, last paragraph above Discussion). Mao et al. teach that the number of DNA/nanoparticles plays a significant role in gene transfection (See pp.12; [0127]). Furthermore, based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was filed, to modify the nanoparticles prepared by Mao et al. with an additional lyophilization step taught by Bordelon et al. to achieve the predictable result of obtaining a composition suitable for pharmaceutical applications. One of ordinary skill in the art would have been motivated to do so because Bordelon et al. taught that preparation methods such as freeze-drying (i.e., lyophilization) are advantageously used to change NP characteristics such as particle size and overall surface charge and have been shown to directly affect the binding efficiencies of the particles to nucleic acids such as antisense DNA oligonucleotides [24, 25] and small interfering RNAs [26] (Introduction section).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Mao et al. and Bordelon et al. as applied to claims 19, 21, 22, 25, 26, 30 and 31 above, and further in view of Buschmann et al. (U.S. Patent 20160130606A1). This rejection was made in the Office action mailed 2/25/2025 and has been rewritten to address the amendment to the claims in the reply filed 8/25/2025.
Applicant Claims
The instant application claims the following:
Claim 32: The pharmaceutical formulation of claim 31, wherein the PEC nanoparticle or plurality of PEC nanoparticles exhibits long term stability at -20 °C for up to 9 months.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Mao et al. is directed to a method, flash nanocomplexation (FNC), for continuous generation of uniform polyelectrolyte complexes (PEC) to optimize the assembly of nanoparticles. (See pp.1; [0009]). Bordelon et al. is directed to the determination of the optimal ratio of plasmid DNA: nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within the nanoparticle complexes (See pp. 1; Abstract).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Mao et al. and Bordelon et al. do not teach the long-term stability of PEC or plurality of PEC nanoparticles at -20° C for at least 9 months. However, this deficiency is cured by Buschmann et al.
Buschmann et al. is directed to a polyelectrolyte complex composition preserving the biological activities of the polyelectrolyte complex following freeze-drying and rehydration. Buschmann et al specifically teaches that “…freeze-drying, also known as lyophilization, is used to increase their long-term stability” (See pp. 1; [0004]). Furthermore, Buschmann et al. discloses that PEI covalently conjugated to polyethylene glycol (PEG) and cholesterol (Chol), PEG-PEI-Chol lipopolyplexes prepared in lactose or sucrose stored as freeze-dried samples for 2 years at -20°C experienced little variation in particle size or biological activity (See pp. 2; [0012]).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Mao et al, Bordelon et al., and Buschmann et al. are all directed to the optimization of PEC nanoparticles with the goal of obtaining optimal nanoparticle activity. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was filed, to modify the FNC method of Mao et al. and the optimization of the ratio of plasmid DNA: nanoparticle of Bordelon et al. with the lyophilization technique of Buschmann et al. to achieve the predictable result of obtaining a composition suitable for maintaining stability of nanoparticle activity. One of ordinary skill in the art would have been motivated to do so because Buschmann et al. teaches that achieving increased stability of the PEC through freeze-drying prevents physical or chemical degradation over long-term storage (See pp. 2; [0013]).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Response to Arguments - 35 USC § 103
With regard to the rejection of claims 22 and 31 under 35 U.S.C. 103 as being unpatentable over Mao et al., and further in view of Bordelon et al., Applicant's arguments filed 8/25/2025 have been fully considered but they are not persuasive.
The response asserts that to establish a prima facie case of obviousness, all of the claim features must be taught or suggested by the prior art. The response asserts that the prior Office action on page 11 acknowledged that Mao does not disclose the hydrodynamic density properties recited in claim 29. Thus, the response asserts that Mao does not anticipate the claims, because a claim is anticipated only if each and every element as set forth in the claim is found, either expressly or inherently described in a single prior art reference.
This argument is not found persuasive for the same reasons given with regard to the rejection under 35 USC 102. Claim 19 is anticipated by Mao et al., and Bordelon et al. is not relied upon to meet any deficiencies with regard to claim 19.
Thus, the rejection is maintained.
With regard to the rejection of claim 32 under 35 U.S.C. 103 as being unpatentable over Mao et al. and Bordelon et al., and further in view of Buschmann et al., Applicant's arguments filed 8/25/2025 have been fully considered but they are not persuasive.
The response asserts that to establish a prima facie case of obviousness, all of the claim features must be taught or suggested by the prior art. The response asserts that the prior Office action on page 11 acknowledged that Mao does not disclose the hydrodynamic density properties recited in claim 29. Thus, the response asserts that Mao does not anticipate the claims, because a claim is anticipated only if each and every element as set forth in the claim is found, either expressly or inherently described in a single prior art reference.
This argument is not found persuasive for the same reasons given with regard to the rejection under 35 USC 102. Claim 19 is anticipated by Mao et al., and Bordelon et al. and/or Buschmann et al. is not relied upon to meet any deficiencies with regard to claim 19.
Thus, the rejection is maintained.
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 rejections were made in the Office action mailed 2/25/2025 and has been rewritten to address the amendment to the claims in the reply filed 8/25/2025:
Instant claim 19 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-27 of copending Application No. 18546222 (‘222). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same composition comprising PEI and polycationic/nucleic acid nanoparticles with the same/overlapping polydispersity index. It is noted that the ‘222 composition represents a species (with regards to the average zeta potential, PDI and concentration of DNA, bound and residual PEI) within the scope of the instantly claimed genus. Thus, the instant claims and the application claims are obvious variants. The difference is that the ‘222 claim set recites a particle size of about 300 to about 500 nm, whereas the instant claim 23 requires a particles size of about 30 to about 130 nm. However, Mao et al. (‘829) discloses an embodiment wherein the generated PEC nanoparticles are about 30 nm to about 45 nm in diameter (See pp. 2; [0020]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claims 26-27 of Application No. ‘222 to include an average size between about 30nm and 130nm to optimize the activity of the nanoparticle. The difference between the instant claim and the ‘222 claim are that the instant claim 27 recites a percent of bound lPEI to total lPEI and claim 26 of ‘222 recites a weight per weight percentage of DNA bound PEI, and residual PEI. However, Mao et al. (‘829) discloses an N/P of 3 for “DNA molecules/NP” prepared by FNC as required by instant claim 27 (See Figure 9A). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claim 26 of ‘222 to include a DNA molecule/NP having an N/P equal to 3 to establish that bound versus free PEI of 70% does not change with an N/P of 3 or greater. The differences between the instant claim and the claim of ‘222 are that instant claim 29 recites a hydrodynamic density of 60-80 Da/nm3 and claim 27 of ‘222 recites an average zeta potential, particle size, polydispersity index (PDI), and a z-average particle size. Mao et al. (‘829) discloses an N/P ratio of 8 and a PDI between 0.05 and 0.2, but more typically 0.05 (See pp. 4 and 8; [0032] and [0092], respectively). Mao et al. also discloses that nanoparticles prepared by FNC have an average positive surface charge of +30mV in water (See pp.12; [0128] and Fig. 12B.) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claim 27 of ‘222 to include an N/P of 8 and a PDI between 0.05 and 0.2, but more typically 0.05 and an average positive surface charge of +30mV in water because the aforementioned properties are inherent to a hydrodynamic density between 60 Da/nm3 to about 80 Da/nm3 which are characteristic of nanoparticles that are sufficient carriers of therapeutics.
Instant claims 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-27 of U.S. Application No. ‘222 in view of Bordelon et al. The ‘222 claim set does not require a particular number of copies of pDNA/NP as required by instant claims 20-22. However, Bordelon et al. teach 1:1 pDNA/NP complex. (See pp. 3, under “3.4 Chi/PLGA-pDNA Complex Formation” and pp. 5, Figure 4(a) gel electrophoresis). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle of ‘222 to include one pDNA per nanoparticle in order to provide the user with a nanoparticle that exhibits a consistent ratio of pDNA to nanoparticles to avoid variations of pDNA coverage of the nanoparticle complexes. Thus, the instant claims and the application claims are obvious variants.
Instant claims 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-27 of copending U.S. Application No. ‘222 in view of Mao et al (‘829). The differences between the instant claims and ‘222 are that instant claims 25-26 do not recite an average zeta potential, particle size, z-average particle size, and a polydispersity index (PDI). However, Mao et al. (‘829) discloses an N/P of 8 for lPEI-DNA complex (See pp. 8; [0032] and figures 2A-2F). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claims 26-27 of ‘222 to include an N/P of 8 of instant claims 26-27 to establish the stability and efficacy of the nanoparticle’s ability to deliver therapeutics.
Instant claim 30 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 4 of copending Application No. ’222. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same composition comprising the same pharmaceutical formulation encompassing the nanoparticle and the same pharmaceutically acceptable carriers, which are polycationic polymers. The ‘222 claims are directed to the method of making the abovementioned composition, whereas the instant claims are directed to the composition. The difference is that the ‘222 method is directed to the development of a gene therapy that is capable of entering a cell, targeting a nucleic acid, and efficaciously delivering a therapeutic composed of the abovementioned composition. However, one of ordinary skill in the art would recognize that if he/she knew how to make the instantly claimed composition (method of ‘222), then it is obvious that the instant composition was known at the time of filing. Thus, the instant claims and the application claims are obvious variants.
Instant claim 31 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25 of copending Application No. ‘222. The differences between the instant claim and the claim of ‘222 is that claim 25 of ‘222 recites a freezing temperature of – 80 °C for storage. However, Bordelon et al. discloses that variations in chitosan type and content, PLGA type, and particle preparation methods (i.e., centrifugation, freeze-drying) have been used to change NP characteristics such as article size and overall surface charge and have been shown to directly affect the binding efficiencies of the particles to nucleic acids such as antisense DNA oligonucleotides [24, 25] and small interfering RNAs [26] (Introduction section). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claim 25 of ‘222 to include a pharmaceutical formulation encompassing the polycationic/nucleic acid nanoparticle and pharmaceutically acceptable carrier because the aforementioned properties make the gene therapy safe to administer to human subjects in need.
Instant claim 32 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25 of copending U.S. Application No. ‘222 in view of Buschmann et al. (U.S. Patent 20160130606A1). The difference between the instant claim and the claim of ‘222 is that the instant claim 32 recites storage of the nanoparticle in -20 ° C for at least 9 months while still exhibiting long term stability. Claim 25 of ‘222 recites storage at -80 ° C as part of the method for lyophilization. However, Buschmann et al. discloses that PEI covalently conjugated to polyethylene glycol (PEG) and cholesterol (Chol), PEG-PEI-Chol lipopolyplexes prepared in lactose or sucrose stored as freeze-dried samples for 2 years at -20°C experienced little variation in particle size or biological activity (See pp. 2; [0012]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticle in claim 25 of ‘222 to include storage parameters including temperature of - 20° C for at least 9 months to result in nanoparticles with long term stability because the storage protocol ensures that the nanoparticles maintain its therapeutic effect when it is administered to a subject.
Response to Arguments - Double Patenting
The provisional rejection of claims 20, 23, 24 and 27-29 on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18546222 (‘222) is moot in view of Applicant’s cancellation of the instant claims in the reply filed 8/25/2025.
With regard to the provisional rejection of claims 19, 21, 22, 25-26 30-32 on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18546222 (‘222), Applicant's arguments filed 8/25/2025 have been fully considered but they are not persuasive. The response requests that the rejection be held in abeyance. Applicant has not overcome the provisional rejection by substantive argument, amendment or a proper terminal disclaimer. Thus, the provisional rejection is maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. 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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Jennifer Dunston
Supervisory Patent Examiner
Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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