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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/17/2025 has been entered.
Status of the Claims
Claims 1-3, 16, 20-21, 23, 27, 29-33, and 99-101 are currently pending.
Claims 1-3, 16, 20, 23, 33, 99, and 100-101 are amended.
Claims 4-15, 17-19, 22, 24-26, 28, and 34-98 are cancelled.
Claims 1-3, 16, 18, 20-21, 23, 27, 29-33, and 99-101 have been considered on the merits.
Withdrawn Rejections
The 35 U.S.C 112(a) Written Description rejection made onto claims 1-3 is withdrawn in light of the amendments made on 09/17/2025.
The 35 U.S.C. 112(b) rejections made onto claims 1-3 and 33 are withdrawn in light of the amendments made on 09/17/2025.
New and Maintained Rejections Necessitated by Amendment
Claim Objections
Applicant is advised that should claim 1 be found allowable, claims 2-3 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).
Drawings
The specification contains description of color with regards to Fig. 9 ([0022]) and Fig. 10 ([0023]). Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 1-3, 16, 20, 27, 29, 31-32, 99, and 101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11-13, 44-52, and 56 of copending Application No. 17426993 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other due to the following.
Claims 1-3 of the instant application limit the method to administering to an individual a pharmaceutical composition comprising a therapeutically effective amount of a gene therapy vector encoding a CLN6 polypeptide which is fully encompassed by claim 46 of ‘993. Further, claims 1-3 further limit the gene therapy to an AAV9 which are also fully encompassed in claim 46 of ‘993. Claims 1-3 limits wherein the nucleotide sequence is SEQ ID NO: 4, which is fully encompassed by claims 11 and 16 of ‘933. Claim 16, 99, and 101 limits wherein the rAAV9 comprises a self-complementary genome which is fully encompassed by claim 20 of ‘933. Claims 1-3 further limits the method of administration to the individual which is full encompassed by claim 47-50 of ‘993. Claim 20 further limits the concentration of viral particles to be administered which is encompassed by claims 51 and 52 of ‘993. Claim 27 limits wherein the individual is less than 10 or less than 1 years old which is encompassed by claim 56 of ‘993. Instant claim 29 limits wherein the individual comprises a CLN6 gene comprising a mutation related to Batten disease which is fully encompassed by claim 46 of ‘993. Instant claims 31-32 limit that the pharmaceutical composition contains a carrier or excipient, and further where the excipient is a non-ionic, low-osmolar compound, a buffer, a polymer, a salt or a combination which is fully encompassed by claims 44 and 45 of the ‘993. Therefore, the instant invention and that of ‘993 are identical and constitute provisional statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 1-3, 16, 21, 23, 27, 29-30, 33, and 99-101 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Amicus Clinical Trial (NCT02725580, made available to the public on 04/01/2016 see page 9 of PDF), referred to as Amicus below, as evidenced by NIH (CLN6 gene listing, Gene ID: 54982) and Cain et al (Molecular Therapy, October, 2019).
With regards to claims 1-3, Amicus teaches a method of preserving photoreceptors/inhibiting retinal degradation/treating visual effects in Batten disease through the administration of a gene therapy vector encoding the CLN6 polypeptide (see pg. 5, “Participant Group/Arm”). Amicus teaches that the gene therapy vector is to be administered intrathecally as required by claims 1-3 (pg. 5, “Participant Group/Arm”). Amicus teaches that the gene therapy vector is scAAV9.CB.CLN6 (also known as AT-GTX-501) which meets the limitations of claims 1-3 as described in the following:
Amicus teaches an AAV9 vector named “scAAV9.CB.CLN6”. The instant specification defines the following statement: “Figure 2 provides the nucleic acid sequence of scAAV9.CB.CLN6 gene cassette (SEQ ID NO: 4)” ([0014]). The instant specification refers to the gene therapy vector as “scAA9.CB.CLN6” over 40 times throughout the specification and examples. One of ordinary skill in the art would understand that gene transfer vectors with identical names would be identical and comprise identical components. However, Cain et al, which is not available as prior art, is being employed as an evidentiary reference to demonstrate that the “scAAV9.CB.CLN6” of the Amicus clinical trial is the identical “scAAV9.CB.CLN6” of the instant specification, which is 100% identical to the instant SEQ ID NO: 4.
Cain states that “to express human CLN6(hCLN6), we designed an scAAV9 viral vector with the hCLN6 gene under control of the CB hybrid promoter, notated as scAAV.CB.CLN6 (Figure S1A)” (pg. 1837, col 1, para 3). Additionally, Cain states that “Taken together, these results indicate the outstanding efficacy of a single, i.c.v. injection of scAAV9.CB.CLN6 into the CSF of P1 Cln6nclf mice and safety of scAAV9.CB.CLN6 in both mice and primates. Based on these promising data, this gene therapy construct has moved into a phase I/II safety trial for CLN6-Batten disease patients (ClinicalTrials.gov: NCT02725580)”. Therefore, Cain demonstrates that the Amicus clinical trial, NCT02725580, employs the identical vector to that of the instant specification which renders the vector of Amicus is 100% identical to SEQ ID NO: 4.
Additional support that the “scAAV.CB.CLN6” of Amicus contains 100% identity to SEQ ID NO: 4, is that Cain teaches the identical components presented in an identical order as the instant SEQ ID NO: 4 in supplemental Fig. 1A, which is reproduced as follows for ease of comparison:
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Cain Figure S1A:
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Instant Figure 1:
Therefore, the scAAV9.CB.CLN6 of Amicus is identical to the scAAV9.CB.CLN6 of the instant invention.
Further, Amicus teaches that the method is performed on an individual that is at least 1 years old, which meets the limitation of an individual of less than 10 years old, as required by claim 27 (pg. 4, “Inclusion Criteria”). Amicus teaches that the individual has been diagnosed with CLN6 Batten disease (also known as vLINCL6, “variant late infantile neuronal ceroid lipofuscinosis 6”) as required by claim 29-30 (pg. 4, “inclusion Criteria”).
Claims 1-3, 21, 23, and 100 contain wherein clauses that recite the intended result of the method(s) rather than requiring an additional step be performed. Claim 1 recites that the method “results in preservation of the photoreceptors of the individual”. Claim 2 recites that the method “inhibits retinal degeneration in the individual”. Claim 3 recites that the methos “treats the visual effects of Batten disease in the individual”. Claim 21 recites that the method results in “a) symptoms of visual failure are prevented or ameliorated, or b) photoreceptor cells in the central retina of the individual are preserved”. Claim 23 recites “wherein the individual comprises a retina comprising a) at least 4 layers of photoreceptor cells 6 months after the intracerebroventricularly or intrathecally administering, b) at least 8 layers of photoreceptor cells 6 months after the intracerebroventricularly or intrathecally administering, c) at least 4 layers of photoreceptor cells 9 months after the intracerebroventricularly or intrathecally administering, or d) at least 8 layers of photoreceptor cells 9 months after the intracerebroventricularly or intrathecally administering”. Claim 100 recites ““wherein the individual comprises a retina comprising a) at least 4 layers of photoreceptor cells 6 months after the intracerebroventricularly or intrathecally administering, b) at least 8 layers of photoreceptor cells 6 months after the intracerebroventricularly or intrathecally administering, c) at least 4 layers of photoreceptor cells 9 months after the intracerebroventricularly or intrathecally administering, or d) at least 8 layers of photoreceptor cells 9 months after the intracerebroventricularly or intrathecally administering”. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claims 1-3 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, Amicus anticipates the claims.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 20, and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Amicus Clinical Trial (NCT02725580, made available to the public on 04/01/2016 see page 9 of PDF), referred to as Amicus below, as evidenced by NIH (CLN6 gene listing, Gene ID: 54982), in view of Kaspar et al (US20170216458A1).
With regards to claims 20 and 31-33, the limitations of the independent claim 1 are taught by Amicus in the 102 rejection above.
Amicus does not explicitly teach the dosage of the gene therapy vector to be about 1x108 to about 1x1015 of the rAAV9 per gram of body weight as required by claim 20. Amicus does not explicitly teach that the gene therapy vector further comprises a pharmaceutically acceptable excipient as required by claim 31. Amicus does not teach that the excipient is a non-ionic, low osmolar compound, a buffer, polymer, a salt, or combination as required by claim 32. Amicus does not teach that the non-ionic, low osmolar compound is iobitrdol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan or a combination as required by claim 33.
However, Kaspar teaches a method of preserving photoreceptors/inhibiting retinal degradation/treating visual effects in Batten disease through the administration of a gene therapy vector encoding the CLN6 polypeptide ([0021], claim 10). Kaspar teaches that the injection can contain anywhere from 1 x106 and 3 x1016 viral particles (vp) per kg of body weight (i.e. 1 x103 and 3 x1013 per gram of body weight) which overlaps with the claimed range and anticipates the overlapped values as required by claim 20 ([0046]). Kaspar teaches that the composition is administered in a non-ionic, low-osmolar compound which can be iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, and/or ioxilan as required by claims 31-33 ([0017]-[0018]). Further, Kaspar teaches that administration of the AAV vector along with the non-ionic, low-osmolar contrast agents improves the survival of mutant mice containing a gene of interest as compared to the administration of the expression vector alone (abstract).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the method of administering an AAV vector containing wild type human CLN6 taught by Amicus with the administration method taught by Kaspar to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Kaspar teaches that administration of the AAV vector along with the non-ionic, low-osmolar contrast agents improves the survival of mutant mice containing a gene of interest as compared to the administration of the expression vector alone (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Amicus with Kaspar because both Amicus and Kaspar teach the administration of the CLN6 polypeptide in AAV vectors.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 09/17/2025 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 7, last 3 para) that the amendments to claims 1-3 limiting the nucleotide sequence to the SEQ ID NO: 4 require the withdrawal of the 35 U.S.C. 102 rejection of record.
This argument is not found persuasive. Amicus teaches an AAV9 vector named “scAAV9.CB.CLN6”. The instant specification defines the following statement: “Figure 2 provides the nucleic acid sequence of scAAV9.CB.CLN6 gene cassette (SEQ ID NO: 4)” ([0014]). Cain states that “to express human CLN6(hCLN6), we designed an scAAV9 viral vector with the hCLN6 gene under control of the CB hybrid promoter, notated as scAAV.CB.CLN6 (Figure S1A)” (pg. 1837, col 1, para 3). Additionally, Cain states that “Taken together, these results indicate the outstanding efficacy of a single, i.c.v. injection of scAAV9.CB.CLN6 into the CSF of P1 Cln6nclf mice and safety of scAAV9.CB.CLN6 in both mice and primates. Based on these promising data, this gene therapy construct has moved into a phase I/II safety trial for CLN6-Batten disease patients (ClinicalTrials.gov: NCT02725580)”. Therefore, Cain demonstrates that the Amicus clinical trial, NCT02725580, employs the identical vector to that of the instant specification which renders the vector of Amicus is 100% identical to SEQ ID NO: 4.
Additional support that the “scAAV.CB.CLN6” of Amicus contains 100% identity to SEQ ID NO: 4, is that Cain teaches the identical components presented in an identical order as the instant SEQ ID NO: 4 in supplemental Fig. 1A, which is reproduced as follows for ease of comparison:
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Cain Figure S1A:
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Instant Figure 1:
Therefore, the scAAV9.CB.CLN6 of Amicus is identical to the scAAV9.CB.CLN6 of the instant invention and the arguments are not found persuasive.
Applicant argues (Remarks, pg. 8, para 1-4) that the amendments to claims 1-3 limiting the nucleotide sequence to the SEQ ID NO: 4 require the withdrawal of the 35 U.S.C. 103 rejection of record.
This argument is not found persuasive for the reasons presented in detail at point 18 of the remarks.
Applicant argues (Remarks, pg. 8, last para spanning para 2 of pg. 9) that the recited effects of administration of a rAAV comprising the nucleotide sequence of SEQ ID NO: 4 are an unexpected result that would not be predictable based on the disclosures of the cited references. Additionally, that “there is no indication in the cited references that an rAAV with a genome comprising the nucleotide sequence of SEQ ID NO: 4 would demonstrate the claim-recited effects of preserving photoreceptors in an individual with Batten disease”.
This argument is not found persuasive. Amicus and Cain demonstrate that SEQ ID NO: 4 is the identical sequence to the vector scAAV9.CB.CLN6. Amicus teaches that this vector is employed as part of a clinical trial wherein the individual receiving treatment has been diagnosed with CLN6 Batten disease (also known as vLINCL6, “variant late infantile neuronal ceroid lipofuscinosis 6”) as required by claim 29-30 (pg. 4, “inclusion Criteria”). Thus, Amicus teaches the claimed method. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claims 1-3 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results. Therefore, the argument is not found persuasive.
Applicant argues (Remarks, pg. 8-9, sentence spanning pg. 8-9) that “[i]t is unknown whether a rAAV vector genome comprising multiple elements would be properly packaged into an infectious particle that effectively transduces the cell”.
Applicant’s argument is not persuasive because it appears to be inconsistent with the well-established understanding in the art that AAV genomes containing multiple genetic elements can be, and routinely are, packaged into infectious particles capable of effective transduction. Additionally, Amicus provides the identical packaging and route of administration of the vector as the instantly claimed methods. Therefore, the argument is not found persuasive.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632