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 in vitro method for detecting in a sample an
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aggregate form of a protein forming
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aggregate aggregates (PAFb); TDP-43 (TAR DNA- binding protein); NaOH at step a2 and HCl at step c2 and RET method in the reply filed on 11/17/2025 is acknowledged. Upon further consideration the species requirement for proteins is withdrawn.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/17/2025.
Claims 1, 4-14 and new claims 18-22 are under consideration in the instant Office Action.
Withdrawn Objections and Rejections
The objection to the disclosure because it contains an embedded hyperlink and/or other form of browser-executable code is withdrawn in view of the amendment submitted on 4/16/2026
The objections to the claim 1 and 12 are withdrawn in view of the amendment submitted on 4/16/2026
The rejection of claims 1-14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn in view of the claim amendments submitted on 4/16/2026
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.
Claims 1, 4-12 and new claims 18-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lehto et al., WO2010/003227 (1/16/2026 PTO-892).
Lehto teaches methods and kits useful to detect the presence of an aggregated form of a target protein in a sample that may also contain the target protein in non-aggregated form (see assay set forth in pages spanning 3-4 and claims 1-3, 4-11, 13-15) and reads on instant claim 1. Lehto teaches that target proteins include beta sheets of beta amyloid, SOD1 and alpha-synuclein (see page 17, lines 15-27) and reads on instant claim 1 and new claim 18. The assay is useful to detect prion aggregates, to diagnose sheep scrapie and human CJD, and aggregated forms of other proteins of clinical interest (see abstract) and reads on instant claims 1, 4 and 8. Lehto teaches the assay entails treating the sample to elevate the pH to at least about 12 (see page 9, lines 27-32) to alter epitopes accessible on the target protein without causing hydrolysis of the target protein; then the treated sample is then neutralized and the neutralized sample is treated by dissociation to release target protein within the aggregate (see page 12, lines 4-16) an reads on instant claims 1 and 8-10. Lehto teaches also teaches using untreated controls to determine that pH elevation yields a protein having an immunoreactivity that is altered relative to an untreated controls (see page 3, lines 16-24) and reads on the second vial requirement of instant claim 1 since the claim calls for comparison between elevate and unelevated pH treatment. The released target protein is then incubated with an agent that binds selectively to an epitope protected from pH elevation. The formation of a binding agent:target protein complex reveals the presence of aggregated protein in the original sample. Lehto teaches using NaOH to increase the pH up to 12 and using HCl as a neutralizing agent to have pH of 6.8 to 8 (see page 1, line 19; page 7, lines 26-31; page 12, lines 4-16) and reads on instant claims 1, 8-10 and new claims 20-22. Lehto teaches that the samples are from body fluids, tissues or homogenates (see page 1, line,5-7; page 16, lines 19-20; page 17, lines 28-31), including brain homogenates (see page 18, lines-12) and reads on instant claims 5-7 and new claim 19. Lehto teaches using detection antibodies including different labels such as radioactive labels, radioisotopes, chemiluminescent labels, cytochromes, and enzymes including horseradish peroxidase and alkaline phosphatase (see page 14, lines, 5-8; page 16, lines 26-28) and reads on instant claims 11-12.
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.
Claims 1, 4-14 and new claims 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Lehto et al., WO2010/003227 (1/16/2026 PTO-892) as applied to claims 1, 4-12 and new claims 18-22 above, and further in view of Kitamura et al., 2015 (1/16/2026 PTO-892).
See Lehto, as discussed above. While Lehto teaches using immunological methods as requires in independent claim 1, Lehto fails to teach the specific RET immunological method of claims 13-14.
Kitamura teaches using conformational analysis of protein aggregation by FRET, a species of RET immunological method (see abstract). Kitamura teaches using Forster/Fluorescence Resonance Energy Transfer (FRET) to observe aggregation prone proteins. Kitamura teaches that FRET analysis of sequestered aggregation-prone proteins have been employed, using gene-encoded fluorescent protein tags. CFP and YFP, a reliable FRET pair of fluorescent proteins, are a typical choice for studies of inclusion bodies (see page 6080, section 2.2.1) as required in instant claims 11-14. Kitamura teaches that this type of imaging was used with proteins associated with pathogenesis of various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) , such as SOD1 which is linked with ALS (see page 6077, 2nd paragraph) as in instant claims 2, 5-7. Kitamura teaches fluorescence imaging techniques provide useful and reliable methods for clarifying the mechanism by which protein aggregation dysregulates proteostasis and, in particular, FRET is useful for detection of oligomerization and aggregation. Kitamura does not specifically teach the instantly claimed method of claim 1.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Lehto and Kitamura The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Kitamura teaches that FRET assay are useful fluorescence imaging techniques which provide useful and reliable methods for clarifying the mechanism by which protein aggregation dysregulates proteostasis. One of ordinary would be motivated to apply the FRET metho taught by Kitamura to the Lehto method to improve the imaging portion of the assay with a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 4/16/2026 have been fully considered but they are not persuasive. Applicant argues that the Lehto reference does not anticipate all of the requirements of the instant claims: specifically the second vial limitation of claim 1. This is not found persuasive because that limitation reads on a control sample to compare to the high pH treated sample of the first vial and Lehto clearly teaches this step of a control sample. Lehto teaches an untreated controls (see page 3, lines 16-24) which calls for the comparison between elevated and unelevated pH treatment. Therefore, this is not found persuasive. Applicant further argues that the Lehto reference does not teach “…adjusting the pH (9.7-13.2) specifically to induce disaggregation of b-sheet protein aggregates.” This is not found persuasive because Lehto explicitly teaches this: at their claim 1, part a) iii: “…treated or contacted with a dissociating agent or dissociating conditions to dissociate aggregated proteins…”. Therefore, this argument is not found persuasive.
Applicant also argues that the Lehto reference is teaching away from the instant claims. This is not fond persuasive because Lehto teaches all of the required active steps and therefore, will produce the same effect whether it is recognized or not by the prior art. MPEP 2145(II) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)” (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”).
MPEP § 2123(I) states “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). Furthermore, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
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.
Advisory Information
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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