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 .
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.
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.
1. Claims 15-20, 22-26 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al., (WO 2000/047186 A1, Aug 17, 2000) (hereinafter Kabanov).
Kabanov teaches a composition, useful for gene therapy purposes, comprising a polynucleotide or derivative thereof and at least one block copolymer, and further comprising a polycation (page 5, lines 9-16). The polycation is a polyamine polymer (claim 3). Polyamines include polyethyleneimine (PEI), polypropyleneimine (PPI), and copolymers thereof (page 18, lines 21-24). The degree of polymerization of the polycationic polymer can preferably be between about 10 and about 10,000. More preferably, the degree of polymerization shall be between about 10 and about 1,000, still more preferably, between about 10 and about 100 (page 14, line 23 – page 15, line 3). Example 24 teaches the synthesis of linear polyimine polycations (i.e., linear PPI and PEI), which are suitable for use in the composition (page 70, lines 15-20). Suitable nucleic acids include antisense nucleic acid molecules, such as, RNA and DNA (page 41, lines 14-19). The composition may include targeting molecules (page 42, lines 3-4) and targeting molecules comprise a lipid group (page 42, lines 11-12). Kabanov teaches methods of treatment comprising administering these compositions to humans and animals (page 8, lines 18-19). The compositions can be used in gene therapy treatments including gene excision therapy (i.e., gene editing) (page 43, lines 19-21). The polynucleotides can be complexed with the polycation and stabilized in the complex demonstrating increased permeability across cell membranes and are well suited for use as vehicles for delivering nucleic acid into cells (page 9, lines 8-10).
Kabanov discloses compositions containing polypropyleneimine (PPI) (page 18, lines 21-24) and nucleic acids (page 41, lines 14-19), wherein the PPI has a degree of polymerization from about 10 and about 100 (page 14, line 23 – page 15, line 3). Together these would provide a composition as claimed instantly. The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP 2143(I)(A).
Regarding the limitation of claim 18 reciting wherein the PEI has a degree of polymerization from about 20 to about 1000, as discussed above, Kabanov discloses wherein the degree of polymerization of the polycationic polymer can be between about 10 and about 10,000 and wherein the polycationic polymer may be a copolymer of PPI and PEI. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed degree of polymerization of PEI in order to arrive at a copolymer of PPI and PEI having a degree of polymerization of the polycationic polymer between about 10 and about 10,000. 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. See MPEP 2144.05(II)(A).
Regarding the limitation of claim 23 reciting wherein the degree of polymerization of PEI to the degree of polymerization of the PPI is from about 1:1 to 1:500, as discussed above, Kabanov teaches that suitable polycation polymers include copolymers of polyethyleneimine (PEI) and polypropyleneimine (PPI), and the degree of polymerization of the polycationic polymer can preferably be between about 10 and about 100. Accordingly, one of ordinary skill in the art would have been able to arrive at the claimed ratio from the degree of polymerization of the polycation copolymer disclosed by Kabanov. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. MPEP 2144.05 A.
2. Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al. (WO 2000/047186 A1, Aug 17, 2000) (hereinafter Kabanov) in view of Saltzman et al. (US 2019/0133962 A1, May 09, 2019) (hereinafter Saltzman).
As discussed above, Kabanov makes obvious the limitations of claims 15 and 20 but does not teach wherein the co-polymer is a random co-polymer.
However, Saltzman discloses 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(propylenimine) ([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]).
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. Kabanov discloses wherein the composition comprises a PPI/PEI copolymer for nucleic acid delivery. 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 Kabanov since it is a known and effective PPI/PEI copolymer for nucleic acid delivery as taught by Saltzman.
3. Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al., (WO 2000/047186 A1, Aug 17, 2000) (hereinafter Kabanov) in view of Slobodkin et al., (US 2006/0093674 A1, May 04, 2011) (hereinafter Slobodkin).
As discussed above, Kabanov makes obvious the limitations of claim 15 but does not teach wherein a molar ratio of nitrogen atoms to phosphorous atoms in the PPI is less than 40.
However, Slobodkin discloses a transfecting composition comprising a nucleic acid and a biodegradable cross-linked cationic multi-block copolymer of linear poly(alkylenimine) (LPAI) and a hydrophilic linker, wherein said LPAI blocks are crossed linked together by said hydrophilic linker with a biodegradable linkage (Claim 13). The linear poly(alkylenimine) (LPAI) can be polyethyleneimine (LPEI) or polypropyleneimine (LPPI) ([0006]). The particle size and zeta potential of the cationic polymer/DNA complexes is influenced by the nitrogen to phosphate (N/P) ratio between the polymer and the DNA molecules in the polymer/DNA complexes ([0051]). Optimal condensation is achieved at N/P ratios between 5/1 to 10/1 ([0052]). The biodegradable cross-linked cationic multi-block copolymers (with a lipid moiety) are able to transfect tumor tissue, thus demonstrating therapeutic potential of these polymers for gene therapy of human diseases ([0055]).
Kabanov teaches compositions useful for gene therapy purposes, comprising DNA and PPI. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art have formulated the PPI of Kabanov to have a molar ratio of nitrogen atoms to phosphorous atoms between 5/1 to 10/1 because particle size and zeta potential of cationic polymer/DNA complexes is influenced by the nitrogen and phosphate ratio and optimal condensation is achieved at N/P ratios between 5/1 to 10/1 as taught by Slobodkin.
Conclusion
Claims 15-28 are rejected.
No claims are allowable.
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/S.J.K./ Examiner, Art Unit 1614
/TRACY LIU/ Primary Examiner, Art Unit 1614