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 .
Election/Restrictions
Applicant’s election without traverse of the species of an ellipsoid zone (EZ) in the reply filed on 11/04/2025 is acknowledged.
Applicant's election with traverse of claims 1-8. 10, 12, 15-17, and 27-33 in the reply filed on 11/04/2025 is acknowledged. The traversal is on the ground(s) that the required form paragraph stating “the election of an invention or species may be made with or without traverse” appeared to be interpreted as requiring both a species and an inventive group election. This is not found persuasive because the requirement for an election of species dated 09/04/2025 did not actually require an inventive group to be elected, just a species election which was made without traverse (the ellipsoid zone (EZ) as measured by SD-OCT). Therefore, the argument is moot.
The requirement is still deemed proper and is therefore made FINAL.
Claim Interpretation
Claims 17 and 27-31 are directed towards an improvement of symptoms associated with Batten disease, with claim 17 specifically stating “a change in baseline”. This is interpreted to mean that the subject was assessed prior to and during treatment, and the change in baseline reflects the impact of said treatment to the subject.
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.
Claims 1, 2, 5-8, 10, 12, 17, 27-31, and 34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hinderer et al. (WO 2018/209205)
Regarding claim 1: Hinderer discloses methods and compositions for treating Batten disease including use of a recombinant adeno-associated virus (hereafter “rAAV”) comprising an AAV capsid and an AAV capsid comprised within the rAAV. The AAV capsid further comprises a vector genome comprising an AAV 5’ inverted terminal repeat (hereafter “ITR”), a promoter, a CLN2 coding sequence encoding a human TPP1, and an AAV 3’ ITR. (57) Furthermore, Hinderer discloses that the composition may be administered via systemic routes, including intraocular. (Pg 24, ln 14-22) This fully reads on claim 1 regarding intraocular administration of an rAAV comprising a vector genome comprising an AAV 5’ ITR, a promoter, a CLN2 coding sequence encoding a TPP1 protein, and an AAV 3’ ITR. In addition to this, Hinderer further discloses that an aspect of the invention is to be used for the treatment of Batten disease caused by a defect in the CLN2 gene via delivery of said rAAV. (Pg 24, ln 3-6) This reads on the method aspect of claim 1 regarding the treatment of ocular manifestations associated with Batten disease.
Regarding claim 2: Example 1 of the invention disclosed by Hinderer details use of a hTTP1 cassette flanked by AAV2 derived ITRs. (Pg 37, ln 16-21)
Regarding claim 5: Claim 5 of the invention disclosed by Hinderer states “the rAAV…wherein the promoter is a chicken beta actin (CBA) promoter”.
Regarding claim 6: Claim 6 of the invention disclosed by Hinderer states “the rAAV…wherein the promoter is a hybrid promoter comprising a CBA promoter sequence and cytomegalovirus enhancer elements”.
Regarding claim 7: Hinderer discloses an embodiment of the invention in which the expression cassette, plasmid, vector, and virus further comprise a rabbit globin poly A component, intron, and CMV enhancer. (Pg 23, ln 31-33)
Regarding claim 8: Hinderer discloses an embodiment of the invention which uses a rabbit beta globin polyadenylation signal as illustrated in Fig. 1A as shown below:
PNG
media_image1.png
266
472
media_image1.png
Greyscale
Regarding claim 10: Hinderer discloses use of a chicken-beta actin intron. (Pg 20, ln 15)
Regarding claim 12: Hinderer discloses an embodiment of the invention comprising cytomegalovirus (hereafter CMV) enhancer elements. (Pg 22, ln 10-12)
Regarding claim 17: Claim 17 is directed towards a change in baseline of the thickness of the ellipsoid zone as measured by SD-OCT. As claim 17 is dependent on claim 1 and claim 1 is directed towards a method of treating ocular manifestations associated with CLN2 Batten disease, it is inherent that in fulfilling the method of claim 1 (treating Batten disease via administration of the rAAV construct), there would be a positive change in baseline seen within the patient. Therefore, it is inherent that the thickness of the ellipsoid zone as measured by SD-OCT would increase from baseline after treatment.
Regarding claims 27-31: Following the discussion of inherency regarding claim 17 above, it is further inherent that the following results would be inherent as a result of administration of the construct of claim 1:
A delay in the onset of retinal degradation compared to the clinical progression with standard of care (claim 27)
A delay in the onset of visual loss compared to the clinical progression with standard of care (claim 28)
Detectable TPP1 expression levels in the vitreous/aqueous humor of the eye are present within three months of administration of the construct of claim 1 (claim 29)
TPP1 expression in the vitreous/aqueous humor was undetectable prior to the administration of the construct of claim 1 (claim 30, this is further inherent as no or severely deficient production of TPP1 is a feature of late-stage Batten disease)
TPP1 in the serum of the subject remain undetectable (claim 31)
Regarding claim 33: Hinderer discloses that the term “subject” as used regarding the claimed invention refers to a mammalian animal, including a human. (Pg 7, ln 25-27)
Regarding claim 34: Hinderer discloses an exemplary AAV.hTTP1co vector which uses an AAV9.CB7.hCLN2. (Pg 8, ln 19-20)
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hinderer et al. (WO 2018/209205) in view of Vandenberghe et al. (Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey, 2011)
The teachings of Hinderer are discussed above. Hinderer fails to teach a dosage concentration of said rAAV that is 2x10^10 genome copies or 6x10^10 genome copies per eye.
Regarding claims 15 and 16: Vandenberghe teaches a method of using either AAV2 or AAV8 vectors carrying a green fluorescent protein (hereafter GFP) transgene administered photoreceptor cells in primates. (Pg 1-2, Abstract) Specifically, Vandenberghe examines how different doses of said AAV impact the level of detectable GFP in the eye and use doses ranging from 10^8-10^11. (Pg 3, Results) It was noted that substantial photoreceptor transduction was achieved at doses starting at 10^9 genome copies for AAV8 and 10^10 genome copies for AAV2 (pg 6, Results) and that transduction does not appear to increase linearly at higher doses. (Pg 8, Discussion). While the specific numbers given by Vandenberghe are 10^8, 10^9, 10^10, and 10^11 and the doses stated by claims 15 and 16 are specifically 2x10^10 genome copies or 6x10^10 genome copies per eye respectively, but per MPEP 2144.05.I,
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Scherl, 156 F.2d 72, 74-75, 70 USPQ 204, 205-206 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934, 24 USPQ 52, 55 (CCPA 1934)(the prior art, which taught about 0.7:1 of alkali to water, renders unpatentable a claim that increased the proportion to at least 1:1 because there was no showing that the claimed proportions were critical); In re Lilienfeld, 67 F.2d 920, 924, 20 USPQ 53, 57 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.).”
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the rAAV comprising a CLN2 coding sequence encoding a human TPP1 protein with the dose ranging between 10^8-10^11 as taught by Vandenberghe to create a composition dosed at either 2x10^10 (claim 15) or 6x10^6 (claim 16) administered to the eye. A person of ordinary skill in the art would have had a reasonable expectation of success and motivation to combine based on the teachings of Vandenberghe, who state that there was no linear increase of transmission of AAV doses than that of 10^9 genome copies for AAV8 and 10^10 genome copies for AAV2.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Hinderer et al. (WO 2018/209205) in view of Schulz et al. (Study of Intraventricular Cerliponase Alfa for CLN2 Disease, 2018)
The teachings of Hinderer are discussed above. Hinderer fails to teach a method of treatment involving intracerebroventricular cerliponase alfa enzyme therapy.
Schulz teaches a study which evaluated the effect of intraventricular infusions of cerliponase alfa every 2 weeks in children with CLN2 disease. (Pg 1898, Methods) Patients were administered via a ventricular reservoir surgically implanted under the scalp with a catheter placed into the cerebral lateral ventricle. (Pg 1900, Treatment) It was found that intraventricular administration of cerliponase alfa every two weeks resulted in a slower rate of decline in motor and language function than those of historical controls. (Pg 1906, Discussion) This reads on use of intracerebroventricular cerliponase alfa enzyme replacement therapy.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hinderer of an rAAV comprising a CLN2 coding sequence encoding a human TPP1 protein with the teachings of Schulz of use of cerliponase alfa therapy to create a co-treatment strategy to combat the progression of Batten disease. A person of ordinary skill in the art would have had motivation and a reasonable expectation of success based on the teachings of Schulz, who state that biweekly use of cerliponase alfa administered intracerebroventricularly slows CNL2 disease related motor and language function decline.
Allowable Subject Matter
Claims 3 and 4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The following are reasons for allowability, barring the conditions necessary for allowance as described above:
Claim 3: Lorens et al. discloses a sequence matching the claimed SEQ ID NO: 2 by 98.7%, but uses said sequence as it relates to angiogenesis and makes no mention of use in treating or preventing Batten disease. Therefore, it is unreasonable to expect a person skilled in the art would be motivated to incorporate it into a construct designed for the treatment of Batten disease. (Col 7, ln 41-50)
Claim 4: There is no prior art available reading on the claimed SEQ ID NO: 3, therefore rendering SEQ ID NO: 3 as novel.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. 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, Tracy Vivlemore, can be reached on (571) 272-2914. 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.
/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638