DETAILED ACTION
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 arguments filed on June 8, 2026 have been received and entered. Claims 1-6, 19, 22-27 have been canceled. Claims 7-18, 20-21 and 28 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-2, 7-13, 15-21 (group I) in the reply filed on November 23, 2020 was acknowledged. Applicant’s election of AAV9 as species for single AAV serotype was also acknowledged. However, upon further consideration, election of species requirement between different species of AAV were withdrawn and all the non-elected species were rejoined with the elected invention.
Claim 14 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 23, 2020.
Priority
This application is a divisional of US application no 15/687,196 filed on 08/25/2017 that is a Continuation of PCT/US2016/019783 filed 02/26/2016, which claims priority from a US provisional application 62/126,271 filed on 02/27/2015.
Claims 7-13, 15-18, 20-21 and 28 are under consideration.
Allowable Subject Matter
The following claims 15, 16 and 21 are drafted by the examiner and considered to distinguish patentably over the art of record in this application, claims 15 and 21 are presented to applicant for consideration:
--A polynucleotide comprising a synthetic nucleotide sequence encoding a human fukutin-related protein (FKRP) having the amino acid encoded by SEQ ID NO:: 2, operably linked to a muscle specific promoter and/or enhancer element, wherein the synthetic nucleotide sequence has at least 90% sequence identity to SEQ ID NO:1, and wherein the GC content of the synthetic nucleotide sequence encoding the FKRP is reduced by about 5% to about 10% relative to the GC content of SEQ ID NO:2, wherein the polynucleotide has increased expression in mammalian cells as compared to identical native FKRP encoded by SEQ ID NO: 2--.
--a method of increasing glycosylation of alpha-dystroglycan (a- DG) in a skeletal muscle cell of a subject in need thereof, said method comprising intravenously administering an effective amount of adeno-associated virus comprising a synthetic nucleotide sequence which encodes a human fukutin-related protein (FKRP) operably linked to a promoter and/or enhancer element that is muscle specific, wherein the synthetic nucleotide sequence consist of SEQ ID NO:1, wherein the FKRP is expressed in skeletal muscle or cardiac muscle of said subject and thereby producing human FKRP and increase glycosylation of a-DG in same cell of the subject in need thereof.--
--A method of delivering a nucleic acid to a subject, comprising intravenously administering to the subject an effective amount of an adeno-associated (AAV) vector comprising a polynucleotide comprising a synthetic nucleotide sequence encoding a human fukutin-related protein (FKRP) operably linked to a muscle specific promoter and/or enhancer element, wherein the synthetic nucleotide sequence has at least 90% sequence identity to SEQ ID NO:1, and wherein the GC content of the synthetic nucleotide sequence encoding the FKRP is reduced by about 5% to about 10% relative to the GC content of SEQ ID NO:2, wherein said subject exhibits increased expression of FKRP in cells of said subject as compared to identical native FKRP encoded by SEQ ID NO: 2.--
Maintained -Claim Rejections - 35 USC § 112 -new matter
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 7-13, 15-18, 20-21 and 28 remain 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.
In the instant case, the recitation of limitation “..has a GC content that is reduced by at least relative to the GC content of SEQ ID NO:2” (claims 21) has a GC content that is reduced by 12% relative to the GC content of SEQ ID NO:2 (claim 28), are considered new matter. There is no explicit or implicit support for a codon optimized FKRP sequence that has a GC content that is reduced by at least 5% relative to the GC content of SEQ ID NO:2 or GC content that is reduced by 12% relative to the GC content of SEQ ID NO:2. In fact, contrary to applicants' assertions, paragraph 77 of the published application directly supports to a sequence, wherein the GC content is reduced by about 5% to about 10% compared to the GC content of SEQ ID NO:2 (e.g., 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or any range or value therein). Thus, at the time the application was filed, an Artisan of skill would not recognize from the disclosure that Applicant was in possession of the synthetic nucleotide sequence has a GC content that is reduced by at least 4.95% or by 12% relative to the GC content of SEQ ID NO:2, as claimed. In case if applicants have evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for a FKRP sequence that has GC content that is reduced by at least 4.95% or reduced by 12% relative to the GC content of SEQ ID NO: 2 as recited in claims 21 and 28 of the instant application (emphasis added). Claims 7-13, 15-18, 20 are included in the rejection because they directly or indirectly depend from the rejected base claims. This is a new matter rejection.
Response to arguments
Applicants traverse the rejection arguing that the instant application provides implicit support throughout, for example, it exemplifies the use of a FKRP coding sequence that has a GC content that is reduced by at least 4.95% and at least 5%.” (emphasis added). Applicants’ arguments have been considered, but are not found fully persuasive.
As stated in previous office action, instant rejection pertains to new matter rejection that is applied in order to prevent applicant from adding information that goes beyond the subject matter originally filed. See In re Rasmussen, 650 F.2d 1212, 1214, 211 USPQ 323, 326 (CCPA 1981); see also MPEP §§ 2163.06 through 2163.07. As such the rejection is not directed to the breadth of the claims. While there is no in haec verba requirement, the claim limitations must be supported in the specification through express, implicit, or inherent disclosure.
As stated in previous office action, instant specification explicitly supports to a FKRP sequence, wherein the GC content is reduced by about 5% to about 10% compared to the GC content of SEQ ID NO:2 (e.g., 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or any range or value therein) (see para. 77 of the published application) (emphasis added). This portion of the specification explicitly provide support wherein the GC content is reduced by: (i) about 5%, (ii) about 10% or (iii) any value in between about 5% to about 10% including one exemplified in the instant application (SEQ ID NO: 1)..
Applicant fails to point explicit or implicit support for a codon optimized FKRP sequence that has a GC content that is reduced by at least 4.5% or reduced by 12% relative to the GC content of SEQ ID NO:2. The claim 21 as such do not limit upper boundary of reduction of GC content relative to the GC content of SEQ ID NO:2. MPEP 2163.05 states “ The failure to meet the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, commonly arises when the claims are changed after filing to either broaden or narrow the breadth of the claim limitations, or to alter a numerical range limitation or to use claim language which is not synonymous with the terminology used in the original disclosure. In the decision in In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976), the ranges described in the original specification included a range of "25%- 60%" and specific examples of "36%" and "50%." A corresponding new claim limitation to "at least 35%" did not meet the description requirement because the phrase "at least" had no upper limit and caused the claim to read literally on embodiments outside the "25% to 60%" range. In the instant case, the claims as amended do not limit the upper percentage of reduced GC content relative to the GC content of SEQ NO: 2. The specification only supports a FKRP sequence, wherein the GC content is reduced by about 5% to about 10% compared to the GC content of SEQ ID NO:2 (e.g., 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or any range or value therein) (see para. 77 of the published application) (emphasis added). Applicant fails to cite any specific portion of the instant specification that provide evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for a FKRP sequence that has GC content that is reduced by at least 4.95% or at least 5% or reduced by 12% relative to the GC content of SEQ ID NO: 2 as recited in claims 21 and 28 of the instant application (emphasis added). Absent evidence to the contrary or applicant pointing for any explicit and/or implicit support in the specification, instant rejection is maintained for the reasons of record.
Withdrawn -Claim Rejections - 35 USC § 112- scope of enablement
Claims 15, 18, 20, 26 and 27 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification fails to provide an enablement for the full scope of the claimed invention. Applicants’ cancellation of claims 26, 27 renders their rejections moot. Applicant’s amendments to the claims and arguments are persuasive, therefore, previous rejection of the claims is hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot.
Withdrawn-Claim Rejections - 35 USC § 112
Claims 7-13, 15-18, 20-21 were 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. In view of Applicants’ amendment and arguments that is found persuasive, therefore, the previous rejection is rendered moot and hereby withdrawn.
Withdrawn-Claim Rejections - 35 USC § 103
Claim 22 were rejected under 35 U.S.C. 103 as being unpatentable over Qiao et al (Molecular Therapy, 2014, 22, 11, 1890-1899 art of record) as evidenced by Vannoy (Human Gene Therapy, 2014, 25, 187-196, IDS), Genbank accession no (AJ314847.1, 07.10.2008, art of record) and Liu (USPGPUB 20110081708, dated 4/7/11) as evidenced by Akhtar et al (Pak. J. Pharm. Sci., Vol.26, No.6, November 2013,.1181-1188). Applicants’ cancellation of claims 22 renders its rejections moot.
Claims 22 and 25 were rejected under 35 U.S.C. 103 as being unpatentable over Qiao et al (Molecular Therapy, 2014, 22, 11, 1890-1899 art of record) as evidenced by Vannoy (Human Gene Therapy, 2014, 25, 187-196), Genbank accession no (AJ314847.1, 07.10.2008, art of record), Liu (USPGPUB 20110081708, dated 4/7/11) as evidenced by Akhtar et al (Pak. J. Pharm. Sci., Vol.26, No.6, November 2013,.1181-1188) and Bancel et al (US20140010861, dated 6/9/2014, EFD/3/9/13 or WO/2013/151663, art of record). Applicants’ cancellation of claims 22 and 25 renders their rejections moot.
Maintained -Double Patenting
Claims 7-13, 15-18, 20-21 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10350305 in view of Qiao et al (Molecular Therapy, 2014, 22, 11, 1890-1899).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass polynucleotide comprising a nucleotide sequence which encodes a human fukutin-related protein (FKRP) operably linked to a promoter and/or enhancer element that is muscle specific or muscle preferred. As such, the ‘305 claims represent a species of the instant broader product claims. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann, 572 F.2d 312, 197 USPQ 5 (CCPA 1978). Additionally, method as claimed in the instant application encompass delivery of a polynucleotide sequence claimed in ‘305. Regarding claims’305 differ from claimed invention by not disclosing intravenously delivering AAV encoding human EKRP having at least 90% sequence identity to SEQ ID NO: 1 that has at least 5% reduced GC content relative to SEQ ID NO: 2. Qiao et al cure deficiency by teaching a method of increasing glycosylation or delivering a subject in need thereof or treating dystroglycanopathy, said method comprising delivering a therapeutic effective amount of AAV9-human codon optimized FKRP to a subject in need thereof (see page 1895, figure 2 and 4). Therefore, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of prior art to modify the method of Qiao by using polynucleotide encoding codon optimized human fukutin-related protein (FKRP) as disclosed in in ‘309, with reasonable expectation of success, before the effective filing date of instant application. Further, the method as claimed encompass the nucleic specifically claimed in ‘305.
Response to argument
Applicant request reconsideration of the rejection in view of arguments against the teaching of Qiao. Applicants’ arguments have been considered, but are not found fully persuasive.
In response, in the instant case, the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass polynucleotide comprising a nucleotide sequence which encodes a human fukutin-related protein (FKRP) operably linked to a promoter and/or enhancer element that is muscle specific or muscle preferred. As such, the ‘305 claims represent a species of the instant broader product claim directed to synthetic nucleotide sequence has at least 89.1% identity to SEQ ID NO:1, and has a GC content that is reduced by at least 4.95% or by 12% relative to the GC content of SEQ ID NO:2. It is well established that a species of a claimed invention renders the genus obvious. Therefore, instant broader claims are anticipated by the synthetic nucleotide of claims of ‘305. In re Schaumann, 572 F.2d 312, 197 USPQ 5 (CCPA 1978). Therefore, rejection is maintained for the reasons of record.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. (i) Afzal-Javan (J Microbiol. 2013 October; 6(8): e7371, 1-7) teaches CAI of 1.0 is considered ideal while a CAI of > 0.8 is rated as good for expression in the desired expression organism. The lower the number, the higher the chance that desired gene will be expressed poorly. The ideal percentage range of GC content is ranged from 30% to 70%. Any peaks out-side of this range will adversely affect transcriptional and translational efficiency.
(2) Exhibit A- Novopro codon optimization tool between Seq ID NO: 2 vs SEQ ID NO: 1, 2024, page 1-3. The data shows that codon optimized FKRP shows at least 5% reduced GC content relative to SEQ ID NO: 2.
(3) Exhibit B Vector Builder codon optimization, 2024, page 1 teaches codon optimized FKRP shows at least 5% reduced GC content relative to SEQ ID NO: 2.
(4) Fath, PloS One, 2011, e17596, 1-14.
THIS ACTION IS MADE FINAL. 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 ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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