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 Response to Election/Restriction Filed and Arguments/Remarks, filed 02 March 2026, have been entered. Claims 21-39 are currently pending. Claims 21, 25, 35, 36, 37, and 38 are independent claims. Applicant’s election without traverse of the invention of Group I, drawn to a nucleic acid, a recombinant adeno-associated (rAAV) expression vector, a mammalian cell, a transgene expression cassette, and a kit, is acknowledged.
Additionally, Applicant’s election without traverse of the following species is acknowledged:
Polypeptides encoded/expressed: a. CNGB3.
Claims 38 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 23-24, 27-28, and 31-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 21-22, 25-26, 29-30, and 35-37 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a CON of U.S. Application No. 17/108,999, filed 01 December 2020 (now ABN), which is a CON of U.S. Application No. 15/636,850, filed 29 June 2017 (now ABN), which is a CON of U.S. Application No. 14/269,723, filed 05 May 2014, now U.S. Patent No. 9,724,429, which claims priority to U.S. Provisional Application No. 61/824,071, filed 16 May 2013.
Thus, the earliest possible priority for the instant application is 16 May 2013.
Information Disclosure Statement
The information disclosure statements filed 03 March 2026 have been considered by the Examiner. Examiner notes the filing of IDS Size Fee assertions for the IDS filed 03 March 2026, as required under 37 CFR 1.98, indicating that no IDS size fee is required under 37 CFR 1.17(v) at this time.
Specification
The disclosure is objected to because of the following informalities: there is a discrepancy between the brief description of the drawing for Figure 3 and the submitted drawing for Figure 3. Figure 3 shows the plasmid names to include the truncated promoter names as “PR1.8”, “PR1.6”, and “PR1.1” whereas the brief description of the drawings refers to the promoters as “PR1.7, PR1.5, and PR1.1” (specification page 5).
Additionally, the Brief Description of Figure 3 recites, ”the locus control region (shown in red)” on page 5 line 32. However, the drawings are presented in black and white, and as such do not have anything shown in red.
Appropriate correction is required. The error may be resolved by either amending the brief description to match or the drawing or by amending the drawing to match the specification. Corrected drawing sheets in compliance with 37 CFR 1.121(d) may be submitted in reply to the Office action to correct the error. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Claim Objections
Claims 2 and 36 are objected to because of the following informalities:
Claim 2 recites the abbreviation “CNGB3” without first writing out the term for which it is an abbreviation. Appropriate correction is required.
Claim 36 recites the abbreviations “CNGB3”, “CNGA3”, and “GNAT2” without first writing out the term for which it is an abbreviation. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 21-22, 25-26, 29-30, and 35-37 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. Claims 22, 25-26, 29-30, and 35-36 are included in this rejection due to their dependence on or encompassing of independent claim 21.
Independent claim 21 recites the limitation "the cone cell specific promoter PR 1.7" in line 1. There is insufficient antecedent basis for this limitation in the claim. As such, the metes and bounds of the claim cannot be determined.
Claim 22 is vague and indefinite in the recitation of “…capable of…” , since this phrase refers to a latent ability, and it is unknown whether the ability is expressed or observed in the invention.
Note, it has been held that the recitation that an element is “capable of” performing a function is not a positive limitation, but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchinson, 69 USPQ 138.
Claim 37 recites, “the expression vector of claim 21” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 21 is directed to a nucleic acid and does not have any recitation of any expression vector. As such, the metes and bounds of the claim cannot be determined.
Claim Interpretation
Claim 21 recites a cone cell specific promoter PR 1.7. The term “promoter” is being interpreted by the Examiner consistent with the definition provided by Applicant in the specification of the instant application. Applicant defines the term “promoter” as:
“a region of DNA that facilitates the transcription of a particular
gene. As part of the process of transcription, the enzyme that synthesizes RNA, known as RNA polymerase, attaches to the DNA near a gene. Promoters contain specific DNA
sequences and response elements that provide an initial binding site for RNA polymerase and for transcription factors that recruit RNA polymerase” (specification page 8 lines 11-15).
Claim 36 recites a transgene expression cassette which comprises “minimal regulatory elements” in line 5. “Minimal regulatory elements” are being interpreted by the Examiner consistent with the definition provided by Applicant in the specification of the instant application. Applicant defines the phrase “minimal regulatory elements” as:
“regulatory elements that are necessary for effective expression of a gene in a target cell and thus should be included in a transgene expression cassette. Such sequences could include, for example, promoter or enhancer sequences, a polylinker sequence facilitating the insertion of a DNA fragment within a plasmid vector, and sequences responsible for intron splicing and polyadenylation of mRNA transcripts. In a recent example of a gene therapy treatment for achromatopsia, the expression cassette included the minimal regulatory elements of a polyadenylation site, splicing signal sequences, and AAV inverted terminal repeats.” (specification page 8 line 28- page 9 line 3).
Therefore, given that claim 36 recites the nucleic acid of claim 21 as an element of the transgene expression cassette in addition to the “minimal regulatory elements”, wherein the nucleic acid of claim 21 comprises the cone cell specific promoter PR 1.7, and that neither claim 36 nor claim 21 recite a vector or intron, “minimal regulatory elements” has been interpreted to encompass at least a polyadenylation sequence.
Claim 36 additionally recites that the transgene expression cassette comprises “a nucleic acid selected from the group consisting of a CNGB3 nucleic acid, a CNGA3 nucleic acid, and a GNAT2 nucleic acid” in lines 4-5. The terms “a CNGB3 nucleic acid, a CNGA3 nucleic acid, and a GNAT2 nucleic acid” have been interpreted to be any fragment of a CNGB3, CNGA3, or GNAT2 gene, including any coding or noncoding sequences without requiring a full coding sequence for the CNGB3, CNGA3, or GNAT2 polypeptides.
The preamble of claim 37 recites “A kit”. The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all the elements of the claim. Any further interpretation of the word is considered an intended use and does not impart any further structural limitation on the claimed subject matter.
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) 21-22, 25-26, 29-30, and 35-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Neitz et al. [WO2011034947A2, published 24 March 2011, IDS, including the accompanying sequence listing].
Regarding claim 21, note that claim 21 recites “A nucleic acid comprising the cone cell specific promoter PR 1.7”. The use of the word “comprising” allows for the inclusion of nucleotide bases in the claimed nucleic acid in addition to the promoter PR 1.7, wherein the promoter PR 1.7 itself consists of the sequence of SEQ ID NO: 3.
Neitz discloses a rAAV vector comprising the nucleic acid sequence of SEQ ID NO: 50, which comprises a cone cell specific promoter sequence identical to the promoter PR 1.7 sequence of SEQ ID NO: 3 of the present application [specification page 1 lines 25-27, page 3 lines 20-22, page 12 lines 6-7, and page 20 lines 6-8, Figure 1A], as shown in the following sequence alignment.
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317
626
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463
584
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Regarding claim 22, Neitz discloses the limitations of claim 21. Neitz discloses that the promoter sequence is specific for retinal cone cells [page 1 lines 27-28, page 2 lines 11-12, page 5 lines 30-31, page 6 line 26- page 7 line 8, page 8 lines 13-18 and 29-31].
Neitz also teaches the sequence of the L opsin promoter (SEQ ID NO: 1) and the sequence of the L/M opsin enhancer (SEQ ID NO: 4) [page 8 lines 10-19], wherein the L/M opsin sequence of Neitz SEQ ID NO: 4 comprises a sequence with 100% identity to nucleotides 1-1230 of instant SEQ ID NO: 3, and wherein the L opsin promoter of Neitz SEQ ID NO: 1 is 100% identical to nucleotides 1231-1724 of instant SEQ ID NO: 3, as seen in the following alignments. As such, the sequence taught by Neitz in SEQ ID NO: 50 is the combination of the L/M opsin enhancer of SEQ ID NO: 4 and the L opsin promoter of SEQ ID NO: 1.
Instant SEQ ID NO: 3 aligned with Neitz SEQ ID NO: 4:
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319
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Instant SEQ ID NO: 3 aligned with Neitz SEQ ID NO: 1:
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Neitz further teaches that the CHOPS2053 promoter used is the 2.1 kb fragment containing the locus control region (LCR) and proximal promoter (PP) upstream of the human X-chromosome opsin gene array, which together are known as pR2.1 and have been shown to target transgene expression to mammalian L/M cones [page 29 lines 25-28, Figure 1]. Neitz also teaches the expression of a transgene under the control of the pR2.1 enhancer/promoter sequence in M cones, wherein transcriptional regulatory elements were selected for preferential expression in M cones but not in S cones [page 24 lines 21-25, Figure 1e, f]. Therefore, Neitz teaches that the promoter is capable of promoting transgene expression in at least M-cone cells and L-cone cells.
Further, the ability to promote expression is an inherent property of the promoter sequence itself. As such, a sequence having 100% sequence identity to the promoter sequence claimed will inherently have the same promoter functions. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Neitz discloses a promoter sequence which has 100% sequence identity to the promoter sequence recited in the instant claims. Accordingly, the promoter sequence disclosed by Neitz will inherently have all of the functions of the instantly claimed promoter. Therefore, Neitz teaches a promoter sequence which is capable of promoting CNGB3 expression in S-cone, M-cone, and L-cone cells absent evidence to the contrary.
Regarding claim 25, Neitz teaches an rAAV expression vector comprising a target nucleic acid sequence operably linked to the nucleic acid comprising the PR 1.7 promoter sequence [page 24 lines 21-25 Figure 1a].
Regarding claims 26 and 29, Neitz discloses the limitations of claim 25. Neitz teaches wherein the target nucleic acid sequence encodes a cyclic nucleotide-gated channel subunit B (CNGB3) polypeptide, wherein a representative sequence of the CNGB3 is provided as SEQ ID NO: 32 [page 9 lines 1-6, page 10 lines 8-9, page 17 lines 3-4]. The sequence listing accompanying Neitz teaches wherein SEQ ID NO: 32 is a Homo sapiens sequence.
Regarding claim 30, Neitz discloses the limitations of claim 25. Neitz teaches wherein the rAAV expression vector is derived from an adeno-associated virus serotype including AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, or AAV8 [page 12 lines 20-22].
Regarding claim 35, Neitz discloses the limitations of claim 25. Neitz teaches a mammalian cell comprising the rAAV expression vector [page 12 lines 8-12 and 28-31, page 24 lines 19-28].
Regarding claim 36, Neitz discloses the limitations of claim 21. Neitz also teaches an expression construct comprising a) the PR1.7 promoter having the L/M opsin enhancer and L opsin promoter with 100% identity to SEQ ID NO: 3 [page 24 lines 21-23, page 29 lines 25-28]; b) a sequence encoding a therapeutic proteins, including a CNGB3 nucleic acid [page 10 lines 8-9, page 44 lines 4-9, claim 23]; and c) minimal regulatory elements (i.e., a polyadenylation sequence) [page 3 lines 19-22, Figure 1a].
Regarding claim 37, as described above under claim interpretation, the term “kit” is being interpreted to encompass any collection of reagents that includes all the elements of the claim. Any further interpretation of the word is considered an intended use and does not impart any further structural limitation on the claimed subject matter. Therefore, a “kit” according to claim 37 is any composition or collection which comprises a nucleic acid comprising the promoter sequence of instant SEQ ID NO: 3 according to claim 21 and instructions for use.
Neitz discloses the limitations of claim 21. Neitz does not explicitly teach a kit comprising a nucleic acid comprising the promoter sequence according to instant SEQ ID NO: 3.
However, addition of “instructions for use” to the product claim does not add additional structure to the product. "Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)" See MPEP 2112.01(III). MPEP 2111.05(I)(B) states, “To be given patentable weight, the printed matter and associated product must be in a functional relationship. A functional relationship can be found where the printed matter performs some function with respect to the product to which it is associated. See Lowry, 32 F.3d at 1584, 32 USPQ2d at 1035 (citing Gulack, 703 F.2d at 1386, 217 USPQ at 404).” Additionally, MPEP 2111.05(I)(B) states, that for “a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” Therefore, the addition of instructions for use to the nucleic acid of claim 21 does not distinguish the nucleic acid from the nucleic acid taught by Neitz and does not add patentable weight to the claimed invention.
Accordingly, by teaching all the limitations of the claims 21-22, 25-26, 29-30, and 35-37 as written, Neitz anticipates the instant invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21-22, 25-26, 29-30, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 9,724,429, hereinafter referred to as the ‘429 patent, in view of Gray et al. [2011, Human Gene Therapy, Vol. 22(9), pages 1143-1153, IDS].
Although the claims at issue are not identical, they are not patentably distinct from each other because the nucleic acid comprising the cone cell specific promoter PR 2.1 comprising the sequence SEQ ID NO: 4 recited in claim 1 of the ‘429 patent fully encompasses with 100% identity the cone cell specific promoter PR 1.7 comprising the sequence SEQ ID NO: 3 recited in independent claim 21 of the instant application. As disclosed in the specification, the PR 1.7 promoter is a 5’ truncated version of the PR 2.1 promoter which is missing about 300 nucleotides from the 5’ end relative to the PR 2.1 promoter (Figure 3). The language of independent claim 21 of the present application recites a nucleic acid comprising a cone cell specific promoter PR 1.7, thus allowing for the inclusion of additional sequences within the nucleic acid molecule. Alternatively, a person of ordinary skill in the art would be motivated to minimize the length of the promoter for improved efficiency and handling of the sequence and would be capable of doing so. Specifically, as taught by Gray, compact promoters take up fewer of the limited nucleotide capacity in a viral vector, e.g., a rAAV vector, leaving more room for the target gene of interest or other sequences (abstract, pages 1143, 1149, and 1152). Further, claims 2, 5-6, and 15-16 of the ‘429 patent limit the nucleic acid of claim 1 with identical limitations as recited in claims 21-22, 25-26, and 35-36 over claim 1 of the present application. Therefore, claims 22, 25-26, 29-30, and 35-37 of the present application are patentably indistinct and/or obvious from claims 1-16 of the ‘429 patent.
Additional comment
Note that the PR 1.7 promoter sequence according to SEQ ID NO: 3 contains two linked discontinuous portions of genomic DNA from the human X chromosome, and thus is not a product of nature.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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