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Claims 7 and 8 are withdrawn from consideration, claims 3, 13, and 18-51 are cancelled, and claims 1-2, 4-6, 9-12, and 14-17 have been considered on their merits.
Withdrawn Objections/Rejections
The claim objections have been withdrawn due to Applicant’s amendment.
The claim rejections under 35 U.S.C. 112(a) have been withdrawn due to the instant
amendment.
The claim rejections under 35 U.S.C. 112(b) have been withdrawn due to the instant
amendment.
The claim rejections under 35 U.S.C. 102(a)(1) have been withdrawn due to the instant
amendment.
The claim rejections under 35 U.S.C. 103 have been withdrawn due to the instant
amendment. However, new grounds of rejection are set forth below.
Claim Rejections - 35 USC § 103 (new)
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 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.
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 1-2, 4-6, 9-12, 14, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Bosch et al. (The Journal of Neuroscience, of record) evidenced by Wiley et al. (Human Gene Therapy, Vol. 27:10, of record) and further in view of Meyer et al. (Molecular Therapy, of record).
Claim 1 it is broadly directed toward delivering any transgene to a retinal cell in any subject by means of administering a gene therapy vector encoding any transgene. It is also noted that the intrathecal delivery as claimed the gene therapy vector encoding the transgene would inherently be delivered to a retinal cell. The limitation directed to the results of expression of the transgene in the retinal cell have not been considered because the limitation does not add structure to the method of delivering a transgene to a retinal cell in a subject it is merely a result of the method. Thus, if the art teach the methods one would expect a similar result.
Regarding claims 1-2 and 17, Bosch et al. teach delivering a transgene to a retinal cell of a subject utilizing a AAV9 vector (p. 9670, Materials and Methods). Bosch et al. teach gene therapy using two self-complementary adeno-associated virus 9 (scAAV9) constructs, scAAV9/β-actin-hCLN3 or scAAV9/MeCP2-hCLN3, to intravenously administer the transgene (delivering a transgene) CLN3 to Cln3Δex7/8 mice (subject) (p. 9670, Material and Methods). Bosch et al. teach the intravenous injection was administered via the retro-orbital sinus (p. 9670, Materials and Methods). Bosch et al. teach the systematic administration of scAAV9 successfully crossed the blood brain barrier to transduce neurons and astrocytes throughout the brain, spinal cord, and eye (pp.9671-9672, Systemic administration of scAAV9 successfully crosses the blood–brain barrier to transduce neurons and astrocytes in juvenile Cln3Δex7/8 mice). Bosch et al. teach both variants of their scAAV9 vector transduced cells in the eye (Bosch et al., Figure 3A). Bosch et al. is silent to the delivering a transgene to a retinal cell, specifically.
However, it would have been obvious to one of ordinary skill in the art to use the vector of Bosch et al. to transduce retinal cells with a reasonable expectation of success because the vectors of Bosch et al. was shown to cross the blood-brain barrier and transduce cells of the eye following intravenous delivery. One would be motivated to use the vector of Bosch et al. to transduce retinal cells because Bosch et al. teach both variants of their scAAV9 vector transduced cells in the eye (Bosch et al., Figure 3A) and CLN3 disease is known in the art to cause CLN3-Associated Isolated Retinal Degeneration. Therefore, it would be reasonable to conceive the vectors of Bosch et al. would be capable of expressing the transgene in a retinal cell or any retinal cells of claim 2.
Bosch et al. is silent to wherein the gene therapy vector is administered to the subject using intrathecal delivery.
However, Meyer et al. teach AAV9-mediated gene therapy for spinal muscular atrophy (SMA) in SMA mice and nonhuman primates utilizing intrathecal injection followed by putting the subjects in the Trendelenburg position (claim 17) (Abstract and p. 481, right column). It would have been obvious to one of ordinary skill in the art to utilize the method of intrathecal delivery of a gene therapy vector of Meyer et al. with the gene therapy vector encoding a transgene of Bosch et al. to deliver a transgene to a retinal cell in a subject with a reasonable expectation of success because Meyer et al. teach their method has provided new guidance toward gene therapy for a wide range of neurodegenerative disorders (Meyer et al., Abstract, p. 478, 2nd column). One would have been motivated to utilize the method of intrathecal delivery of a gene therapy vector of Meyer et al. with the gene therapy vector encoding a transgene of Bosch et al. to deliver a transgene to a retinal cell in a subject because Bosch et al. teach both variants of their scAAV9 vector transduced cells in the eye (Bosch et al., Figure 3A).
Regarding claims 4-6, Bosch et al. teach treatment of a vision-related disorder, juvenile neuronal ceroid lipofuscinosis (JNCL), caused by mutations in the CNL3 gene (Abstract). Bosch et al. teach gene therapy using two self-complementary adeno-associated virus 9 (scAAV9) constructs, scAAV9/β-actin-hCLN3 or scAAV9/MeCP2-hCLN3, to intravenously administer the transgene CLN3 to Cln3Δex7/8 mice (p. 9670, Material and Methods). Wiley et al. disclose juvenile neuronal ceroid lipofuscinosis (JNCL) is commonly known as Batten disease (Wiley et al., p. 835, 1st column). Therefore, Bosch et al. teach where the vision-related disorder is CLN3 Batten disease.
Regarding claims 9 and 10, Bosch et al. teach scAAV9 genomes were engineered to encode human CLN3 cDNA (transgene), which encodes a CLN3 polypeptide (p. 9670, Materials and Methods).
Regarding claim 11, following the rejection of claim 1, Bosch et al. as evidenced by Wiley et al. in view of Meyer et al. teach a method of treating CLN3 Batten disease in Cln3Δex7/8 mice (subject) by administering viral vectors (gene therapy vector) via intrathecal delivery of scAAV9 genomes encoding human CLN3 cDNA, which encodes a CLN3 polypeptide (Bosch et al., Abstract and p. 9670, Materials and Methods).
Regarding claims 12 and 14, Bosch et al. teach the Batten disease is CLN3 disease, the transgene encodes a CLN peptide, and the CLN polypeptide is CLN3 (p. 9670, Materials and Methods).
Regarding claim 16, Bosch et al. teach the gene therapy vector is AAV9 (Abstract).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Bosch et al. (The Journal of Neuroscience, of record) evidenced by Wiley et al. (Human Gene Therapy, Vol. 27:10, of record) and further in view of Meyer et al. (Molecular Therapy, of record) as applied to claim 1-2, 4-6, 9-12, 14, 16, and 17 above, and further in view of Holthaus et al. (Molecular Therapy, Vol. 26 No 5, of record).
Regarding claim 15, Bosch et al. teach the neuron-targeted promoter (MeCP2) used to drive human CLN3 expression restored motor function and decreased glial activation and lysosomal pathology in the ClnΔex7/8 brain (treating Batten disease in a subject) (p. 9680, 1st column, last para.). Bosch et al., therefore, teach reducing one or more symptoms of Batten disease.
Bosch et al. is silent to where the treatment slowed the loss of vision.
However, Holthaus et al. teach rescued photoreceptor degeneration (treating a vision related disorder) in Cln6nclf mice (a subject), a naturally occurring model of CLN6 disease (Batten disease), via intravitreal injections with 7m8.hCLN6 vectors (gene therapy vector encoding a transgene) (p. 1344, Introduction and p. 1346, 7m8-Mediated Supplementation of CLN6 in Bipolar Cells Specifically Rescued the Photoreceptor Degeneration in Cln6nclf mice). Holthaus et al. teach the production of two 7m8.hCLN6 vectors, one carrying the weak PCP2 promoter to drive expression in rod bipolar cells (retinal cells) and one carrying the 4x enhanced Grm6 promoter to drive expression in all ON bipolar cells (p. 1346, 7m8-Mediated Supplementation of CLN6 in Bipolar Cells Specifically Rescued the Photoreceptor Degeneration in Cln6nclf mice). The slowed loss of photoreceptor function reads as slowing a symptom of loss of vision.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the treatment taught by Bosch et al. to slow vision loss in a subject as taught by Holthaus et al. because Bosch et al. teach reducing multiple symptoms of Batten disease. There would have been a reasonable expectation of success for the treatment taught by Bosch et al. to slow vision loss in a subject as taught by Holthaus et al. because Holthaus et al. suggest an ocular AAV-mediated treatment of Cln6nclf mice presents a very similar challenge to deficiencies in CLN3 or other transmembrane defects of neuronal ceroid lipofuscinoses (NCL) providing a proof of concept of gene therapy for CLN3 disease, the most common form of NCL caused by a transmembrane protein defect (Holthaus et al., p. 1350, Discussion). One would have been motivated to treat vision loss with the treatment taught by Bosch et al. to slow vision loss in a subject as taught by Holthaus et al. because Bosch et al. teach both variants of their scAAV9 vector transduced cells in the eye (Bosch et al., Figure 3A).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments, see pp. 6-7, filed 04/23/2025, with respect to the rejections of claims 1-6, 9-11, 13, and 15-16 under 102(a)(1) have been fully considered and are persuasive because the references to not teach the amended limitations pertaining to intrathecal delivery. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Bosch et al., Meyer et al., and Holthaus et al.
Regarding the arguments pertaining to the Meyer et al. reference, while it is noted Meyer et al. do not specifically teach transduction of retinal cells, the method of Meyer et al. do transduce cells of the CNS to include the cortex. Absent evidence to the contrary, one of ordinary skill would expect if a vector was able to transduce cells of the CNS, the same vector would be capable of transducing retinal cells. Additionally, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kaspar et al. (WO 2014/022582, published 02/06/2014, IDS ref.)
Kaspar et al. teach methods and materials useful for intrathecal delivery of polynucleotides to the central nervous system of a patient using rAAV9 as a vector wherein the polynucleotide is delivered to a glial cell. Kaspar et al. teach in some embodiments the polynucleotide is delivered to microglial cells. Kaspar et al. teach this rAAV9 delivered polynucleotide can be used to treat Lysosomal storage disorders including Batten-Spielmeyer-Vogt/Juvenile NCL/CLN3 disease. Kaspar et al. teach the transduction of cells is further increased when a vector of the disclosure is administered via intrathecal administration and is used in combination with a contrast agent and when the patient is put in the Trendelenberg position.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.A.H./Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights