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 Juvenile neuronal ceroid lipofuscinosis (CLN3) disease in claim 2, and a protein in claim 6, in the reply filed on 4/20/2026 is acknowledged.
Priority
This application is a CIP of PCT/US23/65318 (4/4/2023) which claims benefit of 63/362,574 (4/6/2022).
Information Disclosure Statement
The information disclosure statement (IDS) filed on 3/20/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84(u)(1) states “View numbers must be preceded by the abbreviation “FIG.”.
In the current case, the view numbers for Figures 1-21 are preceded by the word “Figure” instead of the abbreviation “FIG.”. View numbers should be updated to recite the abbreviation “FIG.”. Any changes to the drawings should also be reflected in the specification.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. 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. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. 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. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1-2 are objected to because of the following informalities: Claim 1 recites the acronym “TPP1”. Claim 2 recites the acronym “SCMAS”. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “TPP1” is interpreted to mean “tripeptidyl peptidase 1” and the term “SCMAS” is interpreted to mean “subunit c of mitochondrial ATP synthase”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-10 and 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maxfield et al., US 2011/0166074 A1 and as evidenced by Ezaki et al., The Journal of Biochemistry. 2000;128(3):509-16.
Regarding claim 1, Maxfield teaches a method of treating a neurological disorder, wherein a subject in need of treatment for such a disorder is administered a CLN2 therapeutic (Maxfield p. 1 para. 7). The term CLN2 or CLN2 protein is interchangeable with tripeptidyl-peptidase I (TPP1) protein (Maxfield p. 1 para. 11). Maxfield teaches that for amelioration of a neurological disorder, a therapeutically effective amount of a pharmaceutical composition, comprising a CLN2 therapeutic, will restore or enhance TPP1 activity to levels that ameliorate the neurological disorder (Maxfield p. 9 para. 94). Therefore, Maxfield teaches a method comprising administering a therapeutically effective amount of an agent that increases the TPP1 level. As Maxfield teaches the claimed active method steps, i.e. administering a therapeutically effective amount of an agent that increases a level of TPP1 to ameliorate the neurological disorder, it is expected that this method would result in reducing neuroinflammation or correcting brain weight loss in the subject.
Regarding claims 2 and 3, Maxfield teaches that CLN2 may be used as a therapeutic to attenuate the accumulation of abnormal protein deposits associated with neurodegenerative diseases including Juvenile Neural Ceroid Lipofuscinosis, or Juvenile NCL (Maxfield pp. 8-9 para. 78, 86). Juvenile NCL is known in the art to be caused by a deficiency in CLN3 protein and is characterized by an accumulation of subunit c of mitochondrial ATP synthase (SCMAS) in lysosomes of affected cells (see Ezaki p. 509 para. 1, p. 514 Discussion para. 5). Thus, Maxfield teaches that the subject has a disease characterized by accumulation of SCMAS in the lysosomes of cells and characterized by a deficiency in CLN3 protein function, Juvenile NCL.
Regarding claim 4, Maxfield teaches administering an agent (CLN2 protein) that increases the level of TPP1 in affected cells (Maxfield p. 1 para. 7, p. 9 para. 94). TPP1 is known in the art to have the function of reducing accumulation of the hydrophobic protein SCMAS in the lysosomes of affected cells (see Ezaki p. 513 first full para.). Therefore, the agent used in the method of Maxfield, which increases TPP1 levels, is considered to have the function of reducing SCMAS accumulation in affected cells.
Regarding claim 5, Maxfield teaches that the affected cells are neuronal cells (Maxfield p. 9 para. 90).
Regarding claim 6, Maxfield teaches that the agent is a protein, i.e. direct administration of CLN2 as a protein (Maxfield p. 1 para. 13; p. 3 para. 29).
Regarding claim 7, Maxfield teaches that the therapeutic agent is a recombinant human CLN2, or TPP1, protein (Maxfield p. 7 para. 67; p. 14 para. 136).
Regarding claim 8, Maxfield teaches that the CLN2 protein is an inactive proenzyme (Maxfield p. 15 para. 148).
Regarding claim 9, Maxfield teaches that the CLN2 protein may be conjugated to a targeting molecule, and that the targeting molecule includes mannose-6-phosphate, i.e. the CLN2 protein is mannose-6-phosphorylated (Maxfield p. 9 para. 96).
Regarding claim 10, Maxfield teaches that the affected cells receive 10 nM recombinant CLN2 enzyme (Maxfield p. 18 para. 185).
Regarding claim 13, Maxfield teaches that the CLN2 therapeutic may be administered in a controlled release system (Maxfield p. 10 para. 103).
Regarding claim 14, Maxfield teaches that the CLN2 therapeutic may be delivered to lysosomes of affected cells (Maxfield p. 15 para. 145).
Regarding claim 15, Maxfield teaches that the subject is a human (Maxfield p. 9 para. 92).
Claim Rejections - 35 USC § 103
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 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Maxfield et al., US 2011/0166074 A1.
Regarding claims 11 and 12, Maxfield teaches that the CLN2 therapeutic may be administered by injection, including intracranial injection (Maxfield p. 10 para. 101). Maxfield teaches applying 10 nM of recombinant CLN2 enzyme topically to the surface of the exposed brain (Maxfield p. 18 para. 185). Maxfield additionally teaches testing various concentrations of CLN2 protein on murine microglia, specifically 100 nM, 50 nM, 25 nM, and 12.5 nM, which are within the claimed range (Maxfield p. 14 para. 134).
Maxfield does not expressly teach that a therapeutically effective amount in the range of 1-100 nM of recombinant human TPP1 protein is administered via injection, or specifically via intracranial injection, as required by claims 11 and 12.
However, Maxfield teaches that a therapeutically effective amount of the CLN2 therapeutic protein, sufficient to ameliorate the neurological disorder, is delivered, and that the therapeutically effective amount and treatment regimen can be developed for an individual by an ordinary skilled physician, taking into account factors such as the age, sex, size, and physical well-being of the patient; the extent of the disease; previous treatment regimens and the potential for drug interactions; all of which are routinely considered by a physician in prescribing administration of a pharmaceutical agent (Maxfield p. 9 para. 94). Maxfield additionally teaches that intracranial injection is an acceptable method for delivering the therapeutic (Maxfield p. 10 para. 101).
Therefore, it is clear that the amount and concentration of CLN2 being delivered via injection, including intracranial injection, would have been routinely optimized by a skilled artisan based on other conditions. Maxfield clearly teaches that the CLN2 protein is provided in a concentration effective to ameliorate neurological disorders such as Juvenile NCL. Maxfield additionally teaches that optimization of the amount of the therapeutic agent is a common practice based on various parameters which would be known to a skilled artisan, and is therefore a result-effective variable. Result-effective variables would be optimized through routine experimentation by one having ordinary skill in the art. It would have been obvious for a skilled artisan to deliver a concentration of recombinant human TPP1 in the claimed range of 1-100 nM via intracranial injection, especially given Maxfield’s teachings using concentrations within this range administered via different methods, and the routine optimization known to be involved in developing therapeutic amounts of TPP1 protein for treatment of distinct individuals. Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). Therefore, the limitations of claims 11 and 12 are considered obvious in view of Maxfield.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-10, and 14 of copending Application No. 18/854,132 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to methods of treating a subject by administering a therapeutically effective amount of an agent that increases a level or activity of TPP1.
Regarding instant claim 1, claim 1 of ‘132 recites a method of treating a subject having a disease or disorder characterized by accumulation of SCMAS in the lysosomes of affected cells, comprising administering to the subject a therapeutically effective amount of an agent that increases a level or activity of TPP1, to reduce or eliminate symptoms caused by the disease or disorder.
Regarding instant claims 2-15, the limitations of these dependent claims are recited in claims 1-7, 9-10, and 14 of ‘132.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-15 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY F EIX/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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