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 Upon further consideration the species requirement for proteins is withdrawn.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 1-14 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: there are unnecessary capitalizations within the claim; at each start of a step the word is capitalized. This is not proper since it is not the start of a sentence or an abbreviation. Appropriate correction is required.
Claim 12 is objected to for minor informalities: “RET” is an acronym which stands for "Resonance Energy Transfer" and needs to be spelled out in the claim, at least once in the first occurrence. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 are rejected 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 which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is confusing since it used PAFb and PNAFb abbreviations but it is unclear what they stand for since they are not next to the phrase that they are supposed to represent and it is unclear what they are referencing.
The term “likely to contain” in claim 1 is a relative term which renders the claim indefinite. The term “likely to contain” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how the sample would meet the meets and bounds of this claim.
Claim 1 is also indefinite due to the phrase “ appropriate immunological method” limitation. It is unclear what is meant by this limitation since this is a general statement that leaves it to the artisan to determine the way one should measure these protein aggregations without any guidance except a generic guidance of an appropriate immunological method and encompassed any known and unknown methods and one has to determine what is the appropriate method without any guidance an therefore, this limitation is found indefinite.
Regarding claims 1, 6 and 8-10 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 11 and 12 apply the “use” language as transition phrases and leaves the meets and bounds of the claims undefined and therefore, indefinite. Using the appropriate claim language would benefit from the transitional phrases as set forth in MPEP 2111.03 The transitional phrases "comprising", "consisting essentially of" and "consisting of" define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim. Using the correct transitional phrase would clarify exactly what the limitations are requiring as limitation or what is explicitly excluded.
All of the dependent claims do not resolve all of the issues found within the claims they depend from and therefore, continue to suffer from the same deficiencies and are also rejected.
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 1-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lehto et al., WO2010/003227 (instant 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 claims 1-3. 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 1-2, 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. 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 and 8-10. 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) and reads on instant claims 5-7. 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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Lehto et al., WO2010/003227 (instant PTO-892) as applied to claims 1-12 above, and further in view of Kitamura et al., 2015 (instant 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.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Shimonaka et al., 2016 (instantPTO-892) teaches seeding with TDP-43 for protein aggregation of peptide fibrils.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675