DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of t/e previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/2/2026 has been entered.
Status of Application
The Examiner acknowledges receipt of the amendments filed on 3/2/2026 wherein claims 1, 7, 27, 53 and 54 have been amended and claim 22 has been cancelled.
Claims 1-3, 6, 7, 9-14, 18-21, 27-29, 31, 33, 35, 53 and 54 are presented for examination on the merits. The following rejections are made.
Response to Applicants’ Arguments
Applicant’s amendments filed 3/2/2026 overcome the rejection of claims 1, 3, 6, 7, 27-29, 31, 33, 53 and 54 made by the Examiner under 35 USC 103 over Kurosaki et al. (Biomaterials 30, 2009, 2846-2853). This rejection is withdrawn as Kurosaki does not describe their particles as having the ability to target immune cells.
Applicant’s amendments filed 3/2/2025 overcome the rejection of claims 2, 9-12 and 35 made by the Examiner under 35 USC 103 over Kurosaki et al. (Biomaterials 30, 2009, 2846-2853) further in view of Forrest et al. (Pharmaceutical Research, 21(2), 365-371). This rejection is withdrawn for the reason noted under section 4.
Applicant’s amendments filed 3/2/2026 regarding render moot the rejection of claims 18-22 made by the Examiner under 35 USC 103 over Kurosaki et al. (Biomaterials 30, 2009, 2846-2853) further in view of Stephan et al. (US 11872195). It is noted that claim 22 has been cancelled.
Rejections
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.
Claims 1, 3, 6, 7, 13, 14, 18-21, 27-29, 31, 33, 53 and 54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kurosaki et al. (Biomaterials 30, 2009, 2846-2853; of record) in view of Stephan et al. (US 11872195; filed 05/2017; of record) and Na et al. (US 2015/0225723).
Describes a complex of DNA, polyethyleneimine (PEI) and polyglutamic acid for gene delivery systems. The complex is made according to the following Figure:
PNG
media_image1.png
115
340
media_image1.png
Greyscale
(see Figure 1). It is observed that plasmid DNA is complexed with PEI wherein the pDNA/PEI complex is then treated with a polyanion (polyglutamic acid) so as to coat (envelop) the pDNA/PEI surface (see instant claims 1, 7, 27, 29, 31, 33. The PEI used in the complex is to be branched (see Section 2.1, page 2846) (see instant claim 3). The complex comprises a ratio of phosphate (of pDNA): nitrogen (of PEI) of 1:8. Kurosaki states that the DNA/PEI/polyglutamic acid complex is used in method of treating erythrocytes and melanoma cells so as to transfect the target cells with the complexed DNA (see sections 2.4, 2.5, page 2847) (see instant claims 53 and 54).
Regarding claims 13 and 14, Kurosaki teaches that the concentration of the polyglutamic acid was directly related to the uptake of the complex in a concentration dependent manner (See page 2851). Moreover, the charge ratio of phosphate (of pDNA):nitrogen (of PEI):carboxylate (of the anion, polyglutamate) is 1:8:6 and as the charge ratio would be related to the weight ratio of the complex’s component materials, this ratio would suggest that the anionic polyglutamate is present in an amount of 40% ([6/15]*100). Thus, as a) the uptake of the complex is directly related to the presence of the polyglutamic acid and b) 40% of the complex charge/mass could be tired to the polyanion polyglutamic acid, the concentrations of instant claims 13 and 14 would have been obvious. It’s noted that 40% is above the upper range value of instant claim 14 but, as noted before, obviousness exists where claimed ranges are sufficiently close that one would reasonably expect similar properties. See MPEP 2144.05(I).
Kurosaki fails to teach the inclusion of a targeting moiety that targets an immune cell, wherein the particle is internalized by the target cell by receptor mediated endocytosis.
Stephan is directed to the targeted delivery of nucleic acids via nanocarriers. The nanocarrier includes agents that can facilitate internalization by and/or transfection such as PEI/DNA complexes (see column 11, lines 33-35 and lines 57-65). The nanocarrier may be modified to possess a coating so as to impart a negative surface charge. Exemplified coating materials include polyglutamic acid (see column 12, lines 40-42 and column 13, lines 1-5). The nanocarrier may comprise a binding domain so as to bind to a marker of a target cell so as to initiate rapid receptor-induced endocytosis so as to internalize the particle (see column 5, lines 28-65). Although endocytosis is taught by Stephan, such is related to how the product is used and is considered an intended use limitation. See MPEP 2111.02. The binding domain may be an antibody such is a single chain variable fragment antibody (scFv) (see column 22, lines 32-44 and claims 8-9) (see instant claims 18-21). The binding domain can be used to target immune cells (see column 7, liens 1-5) (see instant claim 1). Thus, it would have been obvious to modify Kurosaki’s particle such that the resulting particle comprised an antibody thereby enabling the modified particle to target specific desired cells.
Kurosaki fails to teach the N/P ratio as being at least 15.
Na, like Kurosaki, is directed to gene/cationic polymer complexes for delivering genetic material to a target cell. It is taught that the ion composite of the gene and cationic polymer is to have a N/P ratio of between 0.1-100, preferably from 0.1-50 and that complexes within said range facilitate gene stabilization thereby facilitating an increase in cell absorption efficiency and formation of stable gene nanocomposites (see [0040]). Thus, it would have been obvious to modify Kurosaki’s complex to modulate the N/P ratio to identify a ratio which best suited the stability and absorption efficiency and if such a manipulation found a N/P ratio exceeding 15, then such would have been the result of ordinary skill and common sense. See MPEP 2143(I)(A) which states that combining prior art elements according to known methods to yield predictable results is supportive of obviousness.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claims 2, 9-12 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Kurosaki et al. (Biomaterials 30, 2009, 2846-2853) in view of Stephan et al. (US 11872195; filed 05/2017; of record) and Na et al. (US 2015/0225723) as applied to claims 1, 3, 6, 7, 13, 14, 18-21, 27-29, 31, 33, 53 and 54 above, and further in view of Forrest et al. (Pharmaceutical Research, 21(2), 365-371; of record).
Kurosaki fails to teach the PEI as being acetylated.
Forrest, like Kurosaki, is directed toward using PEI in the transfection of target cells. The PEI is taught to be a known delivery vector of nucleic acid and that modifying PEI to possess acetyl functionalities improves the delivery vectors properties. It is taught that PEI may be modified such that it is 27% acetylated (see abstract and Table 1) and that this acetylated PEI increases the transfection efficiency by 6-fold (see page 369). It would have been obvious to modify the PEI used in Kurosaki’s complex such that it was acetylated (25%), as taught by Forrest, so as to improve the transfection efficiency of the nucleic acid delivery complex. See MPEP 2143(I)(D) which states that it is obvious to apply a known technique (e.g. acetylate PEI) to a known product (e.g. PEI DNA complex) ready for improvement to yield predictable results (e.g. improved gene delivery).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/KYLE A PURDY/Primary Examiner, Art Unit 1611