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
Newly submitted claims 17-18 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: these new claims recite alternative administration from the injection (claim 16), previously recited in claim 1.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 17-18 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Regarding the amendment to claim ,1 reciting a series of 4 alternative detected components/characteristics, the examiner selects detecting decreased Amyloid Beta for further examination.
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 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.
Claim(s) 1-3, 13-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Constantinidis (“Treatment of Alzheimer’s Disease by Zinc Compounds”; 1992; Drug Dev. Res.; 27:1-14; cited in a prior Office action) in view of Novak et al. (US 2016/0151415 A1; 06/02/2016; IDS reference); and Lee et al. (“Zinc Inhibits Amyloid β Production from Alzheimer’s Amyloid Precursor Protein in SH-SY5Y Cells”; 2009; Korean J. Physiol. Pharmacol; 13:195-200).
Claims 7-9 have been canceled
The claims are directed to a method of treating Alzheimer’s disease comprising administering a composition comprising 64Zne or a salt thereof such as an aspartate salt. The claims are further directed to the mode of administration being by injection in the current claim 16 amendment.
Constantinidis teaches administering inter alia intravenously (i.e., by injection) to a patient suffering from Alzheimer’s disease zinc aspartate (page 8, paragraph 5). The administration resulted in improvements in memory, understanding, communication, and social contact in the patient (page 9, paragraph 1).
Constantinidis does not teach administering 64Zn-enriched aspartate, where the enrichment is at least 80% 64Zn. The skilled artisan would have recognized that naturally occurring Zn contains lower relative amount of this isotope (48.63% relative abundance); i.e., some 64Zn-enriched aspartate was injected into the AD subject, but not the claimed levels of “at least 80%” (claims 1, 7) or more (dependent claims 2-3, 8-9) of 64Zn.
Novak et al. teach a pharmaceutical composition in the form of a solution for improving degenerative disease comprising an isotope selected from, inter alia, Zn-64 in an amount of 0-100% (claims 1-2, 5). Degenerative pathologies include Alzheimer disease which are also age related [0007].
It would have been prima facie obvious to one of ordinary skill in the art at the time of the filing of the instant application to utilize the composition of Novak et al. in the method of Constantinidis and have a reasonable expectation of success. One would have been motivated to do so since Novak et al. teach that the composition can be used for treatment of Alzheimer’s disease and Constantinidis teach that zinc compositions treat Alzheimer’s disease. Therefore, the instant claims are rendered obvious by the teachings of the prior art.
Regarding the amendment to claim 1, Constantinidis does not teach detecting decreased Amyloid Beta.
Lee teaches zinc inhibits Amyloid β production from Alzheimer’s Amyloid Precursor Protein in SH-Sy5Y Cells (title). Alzheimer’s disease (AD) is the most common cause of dementia. The pathologic hallmarks of AD are neurofibrillary tangles and senile plaques, the main components of which are tau (a microtubule-associated protein) and amyloid beta peptide (Aβ) respectively )195; 1st paragraph). Lee documents that one effect of zinc influx on Aβ levels was decrease of Aβ40 levels in a dose dependent manner; similarly, concentration of Aβ42 also decreased to a level similar to the level of Aβ 40 (196, right, 4th paragraph).
The reduction of Aβ levels as a result of zinc uptake into cells is consistent with benefits of zinc treatment of AD taught by Constantinidis, and provides a rationale rendering obvious the further detection of decreased Amyloid Beta after obvious administration of administering 64Zn-enriched aspartate. The motivation to include this detection would have been to verify this reduction of Aβ is a result of treatment.
Regarding claim 13 dosing, zinc aspartate was dosed with 3 pills a day, each contains 50 mg of zinc bis (DL-hydrogen aspartate); this would have been an obvious starting point to select zinc-64 aspartate, and the dosing would have resulted in an amount withing the claimed range.
Regarding claim 14, Zn-64 concentrations include 2 mg/mL (Figure 7), rendering obvious this or obvious similar concentrations, within the range of claim 14.
Regarding claim 15, for a typical patient of 65 or 70 kg, 50 mg dosing corresponds to 0.76 or 0.71 mg/kg, rendering obvious the range of claim 15.
Doses, concentrations of aqueous solutions and mg/kg amounts are also obvious as a result of routine optimization, starting with amounts discussed above.
Applicant argues that Constantinidis discloses a method of preventing Alzheimer’s disease, to cure zinc deficiency during a timing window before PHF (paired helical filaments)-NFT (neurofibrillary tangles) production in a subject. Examiner’s review of this reference confirms that treatment of AD by zinc compounds is the title of this review article, reading on the claimed method of treating Alzheimer’s disease.
Regarding the argument that detecting inter alia, decreased Amyloid Beta is required, not detecting formation of PHF-NFT, the current rejection also relies on Lee, which clearly teaches one effect of zinc influx on Aβ levels was decrease of Aβ40 levels in a dose dependent manner; similarly, concentration of Aβ42 also decreased to a level similar to the level of Aβ 40. Thus, the detecting decreased Amyloid Beta is prima facie obvious to add to the method of treating Alzheimer’s disease.
Regarding the allegation that substituting Zn-64 for Constantinidis’s zinc is hindsight. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Regarding the reason to modify, Novak makes clear that modifying isotopes, including ranges that encompass enriching to levels of 80%, 95% and 99% (obvious within the range taught, up to 100%) of light isotopes, including, inter alia, Zn-64 achieve the method outcome, improving degenerative disease and degenerative diseases explicitly encompass Alzheimer’s disease. Thus, Zn-64 is clearly taught to improve AD.
Conclusion
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 TIMOTHY P THOMAS whose telephone number is (571)272-8994. The examiner can normally be reached M-Th 6:30-5:00.
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, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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TIMOTHY P. THOMAS
Primary Examiner
Art Unit 1614
/TIMOTHY P THOMAS/Primary Examiner, Art Unit 1614
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