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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/22/2026 has been entered.
Status of the Claims
Claims 1-14, and 16-20 have been cancelled.
Claims 15, and 21-29 are pending and currently under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the ratio" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claims depending from rejected claims have also been rejected because they incorporate
all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness
concerns outlined above.
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.
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.
Claim(s) 15 and 22-29 are rejected under 35 U.S.C. 103 as being unpatentable over Dohmen et al. (WO2019207061A1, Published 10/31/2019).
Applicant’s Invention
The Applicants claims are drawn to a pharmaceutical composition comprising: a linear polypropyleneimine (L-PPI)/linear polyethyleneimine (L-PEI) co-polymer; and a nucleic acid, wherein the co-polymer has a degree of polymerization from about 20 to 1000, and wherein the ratio of PEI/PPI is about 1:2 to 1:500.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 15, 22-23, 25-27, and 29 Dohmen teaches provided is a composition comprising (i) a nano- or microparticle formulation of a therapeutically active agent (abstract). Dohmen further teaches in example IV Complexes of cationic polymer and mRNA (i.e., nucleic acid) encoding for luciferase were formed using three different polymeric structures: branched poly(ethylenimine) (brPEI, 25 kDa), linear poly(ethylenimine-propyleneimine) (P7, 20 kDa) or linear poly(ethyleneimine-propyleneimine) (P12, 24 kDa). Dohmen also teaches Via modification of the 2-ethyl-2-oxazoline to 2-ethyl-2-oxazine ratio, the resulting ethyleneimine (C2) to propyleneimine (C3) ratio can be modified within the polymer. Dohmen further teaches that the resulting polymers had the following properties:
PNG
media_image1.png
99
699
media_image1.png
Greyscale
. Dohmen continues to teach Complexes were mixed at a final concentration of 0.25 mg/ml_ at the three different N/P ratios 4, 6 and 10 (i.e., less than 40) (pages 55-56). The examiner points out that with regards to the degree of polymerization, the instant specification teaches the degree of polymerization can be calculated using the equation: Mn/M0, where Mn is the number-averaged molecular weight of the polymer and M0 is the molecular weight of the monomer unit (paragraph [0046]). The calculation is as follows: ethyleneimine has a molecular weight of 43.07g/mol and propyleneimine has a molecular weight of 57.10 g/mol. 43.07g/mol + 57.10g/mol= 100.17g/mol. 100.17g/mol/2=50.08 g/mol. So P7 degree of polymerization is 28,300g/mol/50.08g/mol = 565 and P12 degree of polymerization is 33400g/mol/50.08g/mol = 666.9. Therefore, both P7 and P12 (i.e., linear poly(ethylenimine-propyleneimine)) have a degree of polymerization which falls in range with the instantly claimed ranges.
Regarding claim 24, Dohmen teaches the particle formulations of the present invention comprising a complex of a nucleic acid with a cationic polymer or oligomer can also comprise cationic, anionic or neutral lipids (page 18, lines 7-9).
Regarding claim 28, Dohmen teaches furthermore, the uptake or introduction of nucleic acids in cells can be intended to lead to the expression of nucleotide sequences such as genes comprised in the nucleic acid, can be intended for the downregulation, silencing (i.e., gene silencing) or knockdown of endogenous gene expression (page 7, lines 23-25). Dohmen also teaches thus, the suspension composition of the present invention may be for use in RNA-based therapies in cases where the gene defects described in the following table lead to a disease which can then be treated or prevented by a transcript replacement therapy/enzyme replacement therapy with the RNA molecule, preferably the mRNA molecule, of the present invention, wherein the RNA molecule encodes an intact version of the protein or a functional fragment thereof compensating the disclosed defective gene (page 25, lines 34-39). Dohmen further teaches patients to which the composition can be administered comprise animals and humans (page 24, line 21). Dohmen continues to teach that sample preparation for in vivo experiments were kept frozen until nebulization to animals, then nebulized using an Aeroneb Solo Nebulizer (i.e., administered to a veterinary subject) (page 57).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Dohmen does not disclose a single embodiment or example where every limitation recited in the instant claims are taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art because
Dohmen teaches all of the claimed elements. It would have been prima facie obvious at the time
of filing to have to a pharmaceutical composition comprising: a linear polypropyleneimine (L-PPI)/linear polyethyleneimine (L-PEI) co-polymer; and a nucleic acid, wherein the co-polymer has a degree of polymerization from about 20 to 1000, and wherein the ratio of PEI/PPI is about 1:2 to 1:500 because Dohmen teaches these elements as components of their invention.
With regards to claims 15, 23, and 29, wherein the ratio of PEI/PPI is about 1:2 to 1:500, 1:2 to 1:100, and 1:2 to 1:10, it would have been obvious to one of ordinary skill to optimize the ratio of PEI/PPI. One would have understood in view of Dohmen that via modification of the 2-ethyl-2-oxazoline to 2-ethyl-2-oxazine ratio, the resulting ethylenimine (C2) to propyleneimine (C3) ratio can be modified within the polymer. Dohmen further teaches that the resulting polymers had the following properties:
PNG
media_image2.png
124
671
media_image2.png
Greyscale
. Therefore, it would have been obvious to optimize the ratio of PEI/PPI by routine experimentation to adjust the ratio using Dohmen’s teachings as a starting point for the desired results of the ratio of PEI/PPI. Where 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, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Dohmen et al. (WO2019207061A1, Published 10/31/2019) in view of Saltzman et al. (US20190133962A1, Published 05/09/2019).
Applicant’s Invention
Dohmen renders obvious all the limitations of instant claim 15. Applicants claim 21 further adds the limitation wherein the co- polymer is a random co-polymer.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 21, Dohmen teaches provided is a composition comprising (i) a nano- or microparticle formulation of a therapeutically active agent (abstract). Dohmen further teaches in example IV Complexes of cationic polymer and mRNA (i.e., nucleic acid) encoding for luciferase were formed using three different polymeric structures: branched poly(ethylenimine) (brPEI, 25 kDa), linear poly(ethyleneimine-propyleneimine) (P7, 20 kDa) or linear poly(ethyleneimine-propyleneimine) (P12, 24 kDa). Dohmen also teaches Via modification of the 2-ethyl-2-oxazoline to 2-ethyl-2-oxazine ratio, the resulting ethylenimine (C2) to propyleneimine (C3) ratio can be modified within the polymer. Dohmen further teaches that the resulting polymers had the following properties:
PNG
media_image1.png
99
699
media_image1.png
Greyscale
. Dohmen continues to teach Complexes were mixed at a final concentration of 0.25 mg/ml_ at the three different N/P ratios 4, 6 and 10 (i.e., less than 40) (pages 55-56). The examiner points out that with regards to the degree of polymerization, the instant specification teaches the degree of polymerization can be calculated using the equation: Mn/M0, where Mn is the number-averaged molecular weight of the polymer and M0 is the molecular weight of the monomer unit (paragraph [0046]). The calculation is as follows: ethyleneimine has a molecular weight of 43.07g/mol and propyleneimine has a molecular weight of 57.10 g/mol. 43.07g/mol + 57.10g/mol= 100.17g/mol. 100.17g/mol/2=50.08 g/mol. So P7 degree of polymerization is 28,300g/mol/50.08g/mol = 565 and P12 degree of polymerization is 33400g/mol/50.08g/mol = 666.9. Therefore, both P7 and P12 (i.e., linear poly(ethyleneimine-propyleneimine)) have a degree of polymerization which falls in range with the instantly claimed ranges. Dohmen continues to teach that sample preparation for in vivo experiments were kept frozen until nebulization to animals, then nebulized using an Aeroneb Solo Nebulizer (i.e., administered to a veterinary subject) (page 57).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Dohmen does not teach wherein the co- polymer is a random co-polymer. However, this deficiency is cured by Saltzman.
In the analogous art of delivery of therapeutic agents, Saltzman teaches compositions for efficient delivery of therapeutic agents in vivo, formed of polymeric particles from one or more therapeutic agent complexed with a polycationic polymer (abstract). Suitable polycationic polymers include polyethylene imine (PEI) ([0072]) and poly(propyleneimine) ([0073]). Copolymers of two or more polymers described above, including block and/or random copolymers, may also be employed to make the polymeric particles ([0074]). Particles are used to deliver a therapeutic agent ([0080]). Examples of suitable therapeutic agents include DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities ([0083]).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use a random co-polymer in Dohmen’s Complexes of cationic polymer and mRNA (i.e., nucleic acid). Dohmen teaches the compositions in accordance with the invention comprise a nano- or microparticle formulation of a therapeutically active agent, wherein a therapeutically active agent which is preferred for use in the context of the present invention is a nucleic acid. Among nucleic acids as therapeutically active agents comprised in the nano- or microparticle formulations, further preference is given to RNA, more preferably single stranded RNA, and most preferred is mRNA, including modified mRNA (page 3). Dohmen also teaches the therapeutically active agent is a nucleic acid, preferably RNA, more preferably a single- stranded RNA, and most preferably mRNA, the nucleic acid may be delivered to target cells in or via the respiratory tract (page 22, lines 37-39). One would have understood in view of Saltzman compositions for efficient delivery of therapeutic agents in vivo, formed of polymeric particles from one or more therapeutic agent complexed with a polycationic polymer (abstract), wherein suitable polycationic polymers include polyethylene imine (PEI) ([0072]) and poly(propyleneimine) ([0073]), which can be block and/or random copolymers, may also be employed to make the polymeric particles ([0074]), and therapeutic agents include DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities ([0083]). Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated a random co-polymer into the composition of Dohmen since it is a known and effective PPI/PEI copolymer for nucleic acid delivery as taught by Saltzman. The selection of 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 arguments with respect to claim(s) 15 and 21-29 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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.
AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
Prosecution Insights