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 .
Applicant’s amendment of 3/27/26 is entered.
Claims 1-2, 4, 14, and 17-19 are canceled.
Claims 5-6 are canceled.
Claim 19 is newly added.
Claims 1-4 and 7-19 are pending and are considered herein.
Notice: Improper Claim Amendment
Applicant’s amendment of 3/27/26 fails to show the previous claim language which is canceled in Claim 17, i.e., “of claim 8”. The Examiner has forgiven the improper amendment, but Applicant is asked to take care in the future, to avoid non-responsive amendment notices.
Claim Status, Canceled Claims
In light of the cancelation of Claims 5-6, all rejections/objections thereto, are withdrawn.
Claim Objections
In light of the amendments to Claims 2, 4, and 18, the objections to the same are withdrawn.
Applicant is advised that should claim 1 be found allowable, claim 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 7 requires the nanoparticle to contain the gene. However, Claim 1 now requires the nanoparticle contain the gene. Therefore despite a slight difference in wording, these claim have substantially the same scope.
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.
In light of the amendments to Claims 1 and 14, the rejections of Claim 1-4 and 7-18 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, are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
In light of the amendment to Claim 17, making it independent, the rejections of Claims 17-18 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends, are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
In light of the amendment to Claim 1, the rejections of Claims 1-4 and 8-18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, are withdrawn.
To wit, Claim 1 now requires the presence of the gene.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4 and 7-19 remain/are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are broad for the scope of the Markush of active agents in Claim 1.
The specification teaches that these compounds may be used in a process of transfecting a gene in a compacted nucleic acid, into a eukaryotic cell (e.g., paragraph 57). Specifically, it is also taught that inhibiting a protein of the “interactome” of the intake of compacted nucleic acids, can increase transfection efficiency, as it inhibits a protein that inhibits the transfection (e.g., paragraph 2). Table 1 discloses a series of genes encoding proteins that modulate nucleic acid uptake, and may be inhibited with RNAi (pp. 16-37). Table 2 discloses compounds that inhibit proteins that modulate nucleic acid delivery vehicle uptake (pp. 37-41). Table 3 discloses compounds that inhibit proteins that inhibit nucleic acid delivery vehicle uptake (pp. 43-44). The compounds are again disclosed as being used to facilitate transfer of the nanoparticle (paragraph 81). The first example is a method for enhancing nucleic acid transfer, through use of RNAi or pharmacological agents to modulate the interactome, citing figure 1, with an aversion that these approaches have been reduced to practice and can result in as much 50x greater transfection efficiency (paragraph 103). Further, by a method depicted in figure 2, Applicant identified protein interactors of PEG-DNA nanoparticles in the cell, revealing 474 proteins that interact with the nanoparticle listed in Figure 3. Some of them are known to have influence in liposomal gene delivery already. Applicant localizes the location of where the nucleic acids are delivered in table 4 (p. 51). RNAi proposed for helping delivery (paragraph 106), Pharmacological agents are proposed to enhance nucleic acid transfer to the nucleus or ribosome, and 13 compounds (Table 2) are known to modulate proteins that interact, classified by site of action (paragraph 107). Several compounds are discussed (not the compounds of Claim 1). Tables 2 and 3 are discussed to modulate nucleolin-associated nanoparticle uptake, providing proposed methods. The RNA and pharmacological approaches are also discussed as helpful in the laboratory for research and transfection (paragraph 109). Use in treating CF is also taught with proposed use in treating CF. Finally, Applicant argues they have demonstrated NNP interactome proteins may be modulated to increase transfection 10-50 fold, and proposes trials in CF patients, and possible use in other diseases.
However each of the proteins that are part of the “interactome” have various aspects, being multifunctional, and simply inhibiting one protein function would not necessarily inhibit interaction with the nanoparticle. For example, Applicant’s own Figure 1 teaches casein kinase ii has positive and negative effects on different stages of nulceolin-mediated transfection processes. Also, the same protein, casein kinase ii has roles in cell cycle control, DNA repair, circadian rhythm, apoptosis, cell growth and proliferation, and stress signaling (official notice). Which of these functions must be disrupted and which cannot be disrupted to increase transfection? Therefore, the Artisan would not predict which of the associated compounds of claim 1 would actually have a positive or negative effect. Still further, if they have positive and negative effects, the Artisan would not know if it has more positive than negative affect for each drug. And because of the multiple functions of many proteins, the Artisan would not even know which drugs would produce a positive and negative effect, even if they know the functions of the proteins. Finally, suramin is one compound specifically claimed in Claim 1. Lemoine, et al. (2005) “Mechanism of efficient transfection of the nasal airway epithelium by hypotonic shock”, Gene Therapy, 12: 1275-82, teaches, in Figure 6, suramin produces lowered or no difference from the absence of suramin, in nasal cells in vitro.
Thus, given the lack of direct showing of these compounds as working, the questions in the Art as to the effects of the affected protein, whether it affects more positive than negative processes, or if the compound affects a process of the protein unrelated to the transfection, the Artisan would have to experiment to find out which, if any, of these compounds worked.
Such is considered undue experimentation as it is required for every embodiment claimed by Applicant.
Thus, the claims are not considered enabled.
Response to Argument – Enablement
Applicant’s argument of 3/27/26 have been considered but are not found persuasive.
Applicant argues, citing MPEP 2146, that the PHOSITA is not required to perfect the invention, but the Artisan must by enabled to make and use the invention, and that the level of skill is that of an MD or PhD, and Applicant provides detailed teachings, e.g., methods of administering RNAi, and that they may be administered before or after or in combination with the nucleic acid system to enhance uptake of the nucleic acid (p. 24, paragraph 3-p. 25, paragraph 1).
Such is not persuasive. The Examiner has started with the assumption it was enabled, then provided Art written by the PHOSITA and showed how it does not work for one of the embodiments specifically claimed. Applicant has provided no evidence any of the embodiments work, but simply that there exist interactions with elements of the cell. The Examiner has shown that this is insufficient to reasonably predict that any of these molecules will work, much less the whole Markush of species. To wit, it is shown by Lemoine (SUPRA) that suramin does NOT work. Such is sufficient to show at least that embodiment does not work, and by analogy there is no reason to expect that any other member will work.
Applicant argues specific molecular targets can be inhibited to improve uptake, and the the PHOSITA would be able to design and use RNAi targeting these proteins, particularly given the high level of skill of in the art, and it is noted that PEG-lysine conjugates are known to work, and thus sufficient guidance is provided to allow the PHOSITA to carry it out (p. 25, paragraph 2).
Such is not persuasive. There is plenty of implications, and the Art certainly uses elements, however, there is no proof that any embodiment of the claims works, and in fact, Lemoine teaches that suramin probably does not work to improve transfection.
Thus, the claims remain rejected.
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.
Claim(s) 1, 7, and 15-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticiapted by Lemoine, et al. (2005) “Mechanism of efficient transfection of the nasal airway epithelium by hypotonic shock”, Gene Therapy, 12: 1275-82.
Claims 1and 7: Figure 3 evidences transfection of plasmid DNA encoding luciferase, in the presence of suramin, on airway epithelium cells. The plasmid is compacted with cationic polymers that force the supercoiled structure, otherwise it would not fit in to the cell due to size (official notice). The steps having been performed, it is presumed to anticipate the claim.
Claim 15: the office does not have the facilities to determine the shape of the compacted nucleic acid nanoparticle, but it is presumed to spheroidal, absent reason to believe otherwise.
Claim 16: as the PNGVL3-Luc plasmid is approximately 2 kilodaltons in size, and thus, absent reason to believe otherwise, is between 25 and 400 nm (the office does not have facilities to determine this, so it is left for Applicant).
Claim 17: Lemoine teach perfusion with the suramine, along with the plasmid, and thus, they were present in a composition together.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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