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 .
Receipt is acknowledged of an amendment, filed on 04/07/2026, in which claim 1 was amended, claims 4-6 and 30 were previously presented and claim 31 is newly added. Claims 1, 4-6, 30 and 31 are currently pending.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is NON-FINAL.
Priority
Acknowledgment is made of applicant's claim for priority based on a foreign application filed as EP19199697.4 on 09/25/2019.
All claims are given the priority date of 09/25/2019.
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, 4-6, 30 and 31 are rejected 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. 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 1 is drawn to a genus of ribosomal proteins. The rejected claims thus comprise a genus of ribosomal proteins that encompass ribosomal proteins that must be capable of functioning in a gene editing ribonucleoprotein system.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes the gene editing ribonucleoprotein system or gene editing RNP system as a complex formed by a ribosomal protein bound to one or more sequences of nucleic acid that is capable of editing a gene in a mammal [0070]. The specification continues to teach that the ribosomal protein may be a CRISPR nuclease protein, e.g. Cas9, Cas12a, Cas14 or a Cas variant, for example modified versions of nuclease dead (dCas9) [0070]. No description is provided of how a ribosomal protein without a cas nuclease or CRISPR cas system, would be capable of gene editing within a mammal.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of ribonucleoproteins comprising the CRISPR cas system, such as a Cas9 and/or Cas 12 and a guide RNA. The results are not necessarily predictive of any ribosomal proteins. Thus, it is impossible for one to extrapolate from the few examples described herein those ribosomal proteins that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of ribosomal proteins without cas nucleases capable of gene editing within mammals.
Kang et al (Sig Transduct Target Ther 6, 323 (2021); Pgs. 1-22) teaches ribosomal proteins are part of the biosynthesis pathway to create ribosomes, which are the molecular machines that translate messenger RNA (mRNA) into proteins, by synthesizing ribosomal RNA and then modifying and assembling the rRNA with ribosomal proteins to form mature ribosomes (Page 1, Column 1). Kang teaches although ribosomal proteins can have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress, the ribosomal proteins do not comprise the capability of gene editing on their own (Page 1, Abstract and Page 3, Column 2).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 4-6, 30 and 31.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 6, 30 and 31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Green et al (Amer Soc Gene & Cell Therapy. ISSN: 1525-0016. Abstract; April 29 -May 02, 2019; Pgs. 110-111). This is a NEW rejection necessitated by the amendments filed on 04/07/2026.
Regarding claims 1 and 30, Green teaches a nanocomplex comprising a CRISPR-Cas9 ribonucleoprotein system complexed with a hyperbranched PBEA (Page 110, Column 2, Introduction section and Figure 1A). Green teaches the hyperbranched PBEA is a 4-branching poly-beta amino ester polymer formed by reacting a four branching monomer having four reacting sites that comprise a diacrylate and a first and second amine component and react with acrylate or amine groups (Page 110, Column 2, Methods section). Green teaches the CRISPR RNPs were encapsulated into the nanoparticles to create the nanocomplex and delivered to GL261 murine brain cancer cells showing carboxylated branched PBAEs enabled high levels of cytosolic protein delivery and CRISPR gene knockout up to 80%. (Page 110, Column 2 bridging Page 111, Column 1 and Conclusion section).
Regarding claim 4, Green teaches the CRISPR RNPs were encapsulated into the nanoparticles to create the nanocomplex and delivered to GL261 murine brain cancer cells showing carboxylated branched PBAEs enabled high levels of cytosolic protein delivery and CRISPR gene knockout up to 80%. (Page 110, Column 2 bridging Page 111, Column 1 and Conclusion section).
Regarding claim 6, CRISPR RNPs were encapsulated into nanoparticles approximately 180 nm in diameter (Page 110, Column 2, Figure 1 Description).
Regarding claim 31, Green teaches a nanocomplex comprising a CRISPR-Cas9 ribonucleoprotein system complexed with a hyperbranched PBEA (Page 110, Column 2, Introduction section and Figure 1A). Green teaches the CRISPR RNPs were encapsulated into the nanoparticles to create the nanocomplex and delivered to GL261 murine brain cancer cells showing carboxylated branched PBAEs enabled high levels of cytosolic protein delivery and CRISPR gene knockout up to 80%. (Page 110, Column 2 bridging Page 111, Column 1 and Conclusion section). Green teaches the hyperbranched PBEA is a 4-branching poly-beta amino ester polymer formed by reacting a four branching monomer having four reacting sites that comprise a diacrylate and a first and second amine component and react with acrylate or amine groups (Page 110, Column 2, Methods section). Green teaches the carboxylate ligands were synthesized via acrylation of amino acid derivatives to yield a series of acrylated amino acids with varying numbers of carbons between the carboxyl and amide groups (ligands are referred to by the number of carbons) wherein the PBAEs were synthesized via a Michael addition reaction and end-capped with carboxylate ligands such as C5 and C7 alkyls as shown in Figure 1A (Page 110, Column 2, Methods section and Results section).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Green et al (Amer Soc Gene & Cell Therapy. ISSN: 1525-0016. Abstract; April 29 -May 02, 2019; Pgs. 110-111) in view of Bonafont et al (Molecular Therapy Vol. 27, pages 986-998, March 15, 2019; cited in a prior action). This is a NEW rejection necessitated by the amendments filed on 04/07/2026.
The teachings of Green as discussed and applied above.
Regarding claim 5, Green does not teach the CRISPR cas system configured to excise exon 80 of the COL7 Al gene which codes for the collagen VII protein.
Bonafont teaches that using a dual single-guide RNA (sgRNA)-guided Cas9 nuclease delivered as a ribonucleoprotein complex through electroporation, we have achieved very efficient targeted deletion of COL7 Al exon 80 in recessive dystrophic epidermolysis bullosa (RDEB) patient keratinocytes carrying a highly prevalent frameshift mutation (Abstract). This ex vivo non-viral approach rendered a large proportion of corrected cells producing a functional collagen VII variant (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Green to include the specifics of the CRISPR-Cas9 as the gene editing ribonucleoprotein for excision of COL7Al exon 80 as taught by Bonafont because Green teaches it is within the ordinary skill in the art to use a CRISPR system within a nanoparticle complex to be delivered to a cell via a four-branching hyperbranched polymer and Bonafont teaches the use of the Cas9 ribonucleoprotein within a particle complex to excise the COL7A1 exon 80.
One would have been motivated to make such a modification in order to receive the expected benefit of excision of the mutation causing the genetic disorder such as in this case RDEB as taught by Bonafont.
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claims 1, 6 and 30 under 35 U.S.C. 103 as being unpatentable by Chen et al (WO 2019/104058 Al) in view of Gao et al (Biomacromolecules 2016, 17, 3640- 3647) has been withdrawn in view of Applicant’s amendments filed on 04/07/2026.
The previous rejection of claims 4 and 5 under 35 U.S.C. 103 as being unpatentable by Chen et al (WO 2019/104058 Al) and Gao et al (Biomacromolecules 2016, 17, 3640- 3647) further in view of Bonafont et al (Molecular Therapy Vol. 27, pages 986-998, March 15, 2019) has been withdrawn in view of Applicant’s amendments filed on 04/07/2026.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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