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 Status
Claims 1, 8 and 10-15, are pending. Claims 2-7, 9, and 16-21, are cancelled. Claims 1, 8 and 10-15, are examined in the instant application.
All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
This application is claiming the priority benefit of provisional App# 63/150,123 filed 02/17/2021.
Response to Amendments
Status of Objections:
Claim objection for claims 1, 8 and 10-13 are added in view of amendment.
Status of Rejections from action:
The rejection for Claims 1, 8 and 10-13, under 112(b) is added in view of amendment.
The rejection for Claims 1, 8 and 10-13, under 112(a) written description is modified in view of amendment.
The rejection for Claims 1, 8 and 10-13, under 112(a) enablement is modified in view of amendment.
The rejection for Claims 1, 8 and 10-13, under 103 is withdrawn in view of amendment. Because the claims have been amended to include specific deaminases.
The rejection for Claims 14-15, under 103 is modified in view of amendment.
Claim Objections
Claims 1, 8 and 10-13 are objected to because of the following:
In regard to claim 1, Applicant is required to spell out (SCPa, SCPb, and SCPc) acronym the first time using it.
Dependent claims are included, because they do not remedy the issue.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) (Indefinite)
In claims 1, 8 and 10-13, are 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.
In claim 1, the recitation of the NCBI accession code WP_091452319.1, WP_228772027.1 and WP_021798742.1 are unclear. Because external database records (such as NCBI accession numbers) are dynamic and subject to future alteration, reannotation, or deletion, the scope of the claim cannot be determined with reasonable certainty. Accordingly, the boundaries of the claimed subject matter are unclear. Applicant has been advised to include SEQ ID No. identifiers in interview.
Claims 8 and 10-13 are rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
Applicant is advised to amend the claims appropriately.
Claim Rejections - 35 USC § 112(a)(Written Description)
Claims 1, 8 and 10-13 REMAIN 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.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant only describes using a construct comprising a chloroplast targeting peptide, TALE array protein, DddA-derived cytosine base editors (DdCBEs): DddA (WP_080324253.1) obtained from B. cenocepacia, SCPa (WP_091452319.1) obtained from A. iranica, SCPb (WP_228772027.1) obtained from A. iranica and SCPc (WP_021798742.1) obtained from P. acidifaciens (See paragraphs [0078]-[0079]) and 1 uracil glycosylase inhibitor (UGI) (see pages 23-24 and fig. 1) targeting the chloroplast. Additionally, the specification describes generating plants with said constructs (pg. 24 paragraphs [0080]-[0081]).
The claimed invention lacks adequate written description for the following reasons.
The claims encompasses deaminases having the NCBI accession code WP_091452319.1, WP_228772027.1 or WP_021798742.1. This sequence constitutes essential material under MPEP 608.01(p) because the claims require these specific deaminase to construct the claimed invention. Third party database records are dynamic and subject to change, deletion, reference to an accession number alone fails to provide a permanent sequence structure of the claimed deaminase. Failure to describe makes unpredictable for one skilled in the art to make and identify the required deaminase if said NCBI accession numbers are deleted.
For example, SCPb deaminase encoded by NCBI accession code WP_228772027.1 is currently suppressed and unavailable for one skilled in the art to access the structure. Therefore, further highlighting the issue of claiming the NCBI accession instead utilizing SEQ ID No. identifiers.
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Because of the lack of a description and representative number of structures/sequences, the absence of the sequence information, and being only identifiable via gene name, one skilled in the art would not know the structures that would arrive to the recombinant fusion protein. Moreover, the lack of sufficient identifying characteristics and undisclosed sequence structure the Applicant fails to show possession of the invention as claimed.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111.
Response to Arguments
Applicant’s arguments with respect to claims 1, 8 and 10-13 have been considered but are unpersuasive. The Applicant primarily argues that adding NCBI accession code WP_091452319.1 obtained from Actinokineospora iranica, a SCPb deaminase encoded by NCBI accession code WP_228772027.1 obtained from Actinokineospora iranica, or a SCPc deaminase encoded by NCBI accession code WP_021798742.1 obtained from Propionibacterium acidifaciens is sufficient written description and possession of the instant invention. However, the disclosure of the NCBI accession numbers are not sufficient written description, because third-party database records are dynamic and subject to future change, cancellation, or removal, an accession number alone does not ensure permanent public access to the essential material (MPEP 2422.03(III)). Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1, 8 and 10-13 REMAIN rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because arguably the specification, while being enabling for making and using a recombinant fusion protein comprising a chloroplast targeting peptide, TALE array protein, DddA (WP 080324253.1) obtained from B. cenocepacia, SCPa (WP_091452319.1) obtained from A. iranica, SCPb (WP_228772027.1) obtained from A. iranica and SCPc (WP_021798742.1) obtained from P. acidifaciens (see paragraphs [0078]-[0079]) and 1 UGI, does not reasonably provide enablement when said NCBI accession numbers are modified in any way shape of form, because it is not a permanent sequence listing/deposit. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
“The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the specification of a patent enable any person skilled in the art to which it pertains to make and use the claimed invention. Although the statute does not say so, enablement requires that the specification teach those in the art to make and use the invention without ‘undue experimentation.’ In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original); see also In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’”) “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” Wands, supra.
Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. Factors to consider include , but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Id. Applicant’s disclosure is as set forth above. The claimed invention is not enabled for the following reasons. To comply with 35 USC 112(a) enablement, one skilled in the art must be able to make and use the claimed invention.
(A) The breadth of the claims
The breadth of the claims encompasses a recombinant fusion protein that targets either a plant chloroplast or mitochondria comprising a TALE array protein, DddA-derived cytosine base editors (DdCBEs): SCPa (WP_091452319.1) obtained from A. iranica, SCPb (WP_228772027.1) obtained from A. iranica and SCPc (WP_021798742.1) obtained from P. acidifaciens (see paragraphs [0078]-[0079]), and 1 UGI (see pages 23-24 and fig. 1) targeting the chloroplast.
(B) The nature of the invention.
The nature of the claimed invention is directed to a recombinant fusion protein that targets either a plant chloroplast or mitochondria using a TALE array protein, a SCP deaminase, and a UGI on the N-terminus.
(C) The state of the prior art
The state of the prior art does teach on SCPa (WP_091452319.1) obtained from A. iranica, SCPb (WP_228772027.1) obtained from A. iranica and SCPc (WP_021798742.1) obtained from P. acidifaciens deaminase. However, the structures are not readily available for one skilled in the art to access.
For example, SCPb deaminase encoded by NCBI accession code WP_228772027.1 is currently suppressed and unavailable for one skilled in the art to access the structure. Therefore, if one cannot access the accession number how is one to know the structure.
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(D) The level of one of ordinary skill
The level of one of ordinary skill in the art is high as far as using deaminases in fusion proteins but not the genus of deaminases or the structure required to confer functional activity.
(E) The level of predictability in the art
The level of predictability in the art for the deaminase is unclear, because yes one skilled in the art can access these structure, but it is uncertain if these structures will be available in the future. Therefore, making highly unpredictable one skilled in the art to use and access said structures.
(F) The amount of direction provided by the inventor
The amount of direction provided by the inventor is limited to the life of the NCBI accession number, as seen above the accession number is not readily available one skilled in the art. Therefore, the specification does not provide enough guidance for one skilled in the art to replicate making and using the recombinant fusion protein, because the deaminase is not readily available.
(G) The existence of working examples
The specification does provide working examples using a DddA-derived cytosine base editors (DdCBEs) and TALENs/DddA deaminase domain (TALCDA), which are unclear what species of deaminase/NCBI accession are used in paragraphs [0078]–[0079]. Additionally, the only other example of an SCP deaminase appears in a research plan diagram (fig. 7) rather than a functional working example. Moreover, the Applicant fails to specify the exact SCP deaminase used, rendering it impossible to identify.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claimed invention lacks adequate enabling guidance for the following reasons.
The Applicant claims SCPa deaminase encoded by WP_091452319.1, a SCPb deaminase encoded by WP_228772027 .1, or a SCPc deaminase encoded by WP_021798742.1, however these NCBI listings are considered essential material under MPEP 608.01(p), because they are necessary to construct and practice the claimed expression vector. Because third-party database records are dynamic and subject to future change, cancellation, or removal, an accession number alone does not ensure permanent public access to the essential material (MPEP 2422.03(III)). Without the specific sequence structure provided in the specification as filed one skilled in the art would require an undue amount of experimentation to identify and locate said deaminase if an alteration of the claimed NCBI accession number would occur.
The specification fails to TEACH, or fails to provide GUIDANCE for making the recombinant fusion protein to target and modify the chloroplast or mitochondria. The lack or guidance and the lack of working examples means one skilled in the cannot make and use a said deaminase.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding the structure of NCBI accession code WP_091452319.1, WP_228772027.1 or WP_021798742.1 deaminases which confer functional activity, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Response to Arguments
Applicant’s arguments with respect to claims 1, 8 and 10-13 have been considered but are unpersuasive. The Applicant primarily argues that adding NCBI accession code WP_091452319.1 obtained from Actinokineospora iranica, a SCPb deaminase encoded by NCBI accession code WP_228772027 .1 obtained from Actinokineospora iranica, or a SCPc deaminase encoded by NCBI accession code WP_021798742.1 obtained from Propionibacterium acidifaciens enables any person skilled in the art to make and use the invention commensurate in scope with claims. However, the disclosure of the NCBI accession numbers are not sufficient enabling guidance, because third-party database records are dynamic and subject to future change, cancellation, or removal, an accession number alone does not ensure permanent public access to the essential material (MPEP 2422.03(III)). Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 14-15 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over Kim et al., (Chloroplast and mitochondrial DNA editing in plants, 20 January 2021, PREPRINT (Version 1) available at Research Square (previously cited)).
Claim interpretation: Claims 14-15 are open to the entire genus of deaminases, so any species of deaminase found in the art would read on the claims.
In regards to claims 14-15, Kim et al. teach a method to edit a plant chloroplast DNA (pg. 2, top para.). Additionally, Kim et al. teach the recombinant fusion protein structure which includes sequences for “a chloroplast transit peptide (CTP) or a mitochondrial targeting sequence (MTS), the TAL effector N- or C-terminal domains, split-DddAtox halves (G1333N, G1333C, G1397N and G1397C) and UGI, which are codon-optimized for expression in dicot plants” (pg. 2, top para.). Furthermore, Kim et al. teach the results of the “best-performing cp-DdCBE pair (Left-G1397-N + Right-G1397-C) induced C∙G-to-T∙A conversions in the 15-bp spacer region between the two TALE array-binding sites at frequencies of 30.2% in lettuce protoplasts and 8.6% in rapeseed protoplasts” (pg. 2, 2nd to last para.).
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to perform the method of editing a plant chloroplast nucleic acid of Kim et al. utilizing recombinant fusion protein paired with deaminase because suggests doing so.
One would have a reasonable expectation of success in doing so because Kim et al. teach the successful application of recombinant fusion proteins comprising a plant chloroplast targeting peptide, a TALE array protein, and a deaminase, and an UGI wherein the recombinant fusion protein has high catalyzing frequencies of a C•G to T•A conversion in the target chloroplast DNA (pg. 2, 2nd to last para.).
Subject matter free of the prior art
In regard to claims 1, 8 and 10-13 are free of the prior art. The closest prior art is from Kim et al., (Chloroplast and mitochondrial DNA editing in plants, 20 January 2021, PREPRINT (Version 1) available at Research Square (previously cited)) that teaches similar construction design, but fails to teach utilizing NCBI accession code WP_091452319.1, WP_228772027.1 or WP_021798742.1 deaminases.
Conclusion
No claims are 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.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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