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 .
Status of Claims
The claim set submitted on 11 JANUARY 2024 is acknowledged and considered. The claim set submitted on 11 JANUARY 2024 is the most recent claim set.
In the claim set, Claims 2-7, 10-11, 17-55, 61-62, 64, 68-69 and 73-85 are ‘Canceled’; Claims 1, 8, 9, 12-16, 56, 58, 59, 60, 63, 65, 66, 67 and 70 are ‘Currently Amended’; Claims 57, 71 and 72 are ‘Original’.
Current pending claims are Claims 1, 8, 9, 12-16, 56-60, 63, 65-67 and 70-72 and are considered on the merits below.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 JUNE 2024 was filed. The submission 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 as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: all reference characters in Figure 7. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) 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. 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.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: all reference characters in the description of Figure 7, [0103-0109, 0113, 0114]. 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. 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.
Specification
The disclosure is objected to because of the following informalities:
At the end of [0009], it appears to be a fragment of a sentence, which ends with ‘for early diagnosis of’. Examiner believes a missing phrase or word should be inserted here.
The use of the term DYNABEADS®, ANASPEC™, [0130], DIONEX®, [0132], BIOGRAPH®, [0141]which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 13 is objected to because of the following informalities: There is a period missing at the end of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 56 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a method for determining a likelihood that a subject has Alzheimer's Disease , an abstract idea without significantly more. The claim(s) recite(s) : a method for determining a likelihood that a subject has Alzheimer's Disease, comprising:(a) via immunoprecipitation, enriching a biological sample of said subject for proteins that are associated with said Alzheimer's Disease; (b) directing a liquid medium comprising at least a subset of said proteins enriched in (a) to flow through a microfluidic device to separate individual proteins of said at least said subset of said proteins from one another; (c) via a targeted mass spectrometry (MS), selecting a preferred charge state of at least one of said individual proteins and generating signals assignable to said individual proteins or fragments thereof; and (d) determining, based at least in part on said signals, said likelihood that said subject is positive for said Alzheimer's Disease in Claim 1.
The claim(s) recite(s) : method for determining a likelihood that a subject has Alzheimer's Disease, comprising:(a) via immunoprecipitation, enriching a biological sample of said individual for proteins that are associated with said Alzheimer's Disease; (b) directing a liquid medium comprising at least a subset of said proteins enriched in (a) to flow through a microfluidic device to separate individual proteins of said at least said subset of said proteins from one another; (c) via a targeted mass spectrometry (MS), selecting a preferred charge state of at least one of said individual proteins, and generating signals assignable to said individual proteins or fragments thereof, wherein said individual proteins have not been subjected to an enzymatic digestion process prior to (c); and (d) determining, based at least in part on said signals of (c), said likelihood that said subject is positive for said Alzheimer's Disease in Claim 56.
The analysis below is the same for Claims 1 and 56.
The limitation of steps (d) occurs where determining step is performed is a comparison step which recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings in the 2019 PEG, and a law of nature). The determining and assessing for a likelihood are abstract ideas as they encompass observations and evaluations. These claims identify the recited exception as an abstract idea. Determining, assessing and comparing are all abstract ideas in the form of mental processes. These steps are data gathering to be used in the abstract idea and are insignificant extra solution activities. Once step (d) is performed, as a process, that under its broadest reasonable interpretation, covers performance of the limitation of the mind. This limitation sets forth a judicial exception and can be performed by a human using mental steps or basic critical thinking which is an abstract idea, MPEP 2106.040 (a)(2)(III).
This judicial exception is not integrated into a practical application because the elements of step (d) does not impose any meaningful limits on practicing the abstract idea. The claim is directed to an abstract idea. While, in some dependent claim include further limitations of the determining steps, these steps do nothing with the findings. In addition, these additional steps are WURC as taught by the prior art, see below. Therefore, there is no application of the abstract ideas much less a particular practical application.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to the abstract idea into a practical application, the steps (a)-(d) are not an inventive concept as taught by the prior art.
The steps (a)-(d) do not appear to have ‘significantly’ more as all steps are WURC (well understood routine and conventional). In a method of method for determining a likelihood that a subject has Alzheimer's Disease or is positive for the disease, steps (a) – ( c) are recited at a high level of generality such that it amount to insignificant presolution activity, e.g. mere data gathering is necessary to use to re-assess (compare), in addition steps (a) – ( c) are WURC as taught by the prior art and as seen in the rejection below. Since it is claimed at a high level of generality, there is no meaningful limitation claimed, such as a particular or unconventional machine or transformation of a particular article.
The claims are not patent eligible.
In addition, dependent claims 8, 9 and 12-16 merely recite limitations of the determining step and limitation of the type of proteins that are used as biomarkers. These steps and type of proteins as biomarker for Alzheimer’s Disease are well known in the art as seen in rejection below.
Similarly, dependent claims 57-60, 63, 65-67 and 70-72 merely recite limitations of the determining step and limitation of the type of proteins that are used as biomarkers. These steps and type of proteins as biomarker for Alzheimer’s Disease are well known in the art as seen in rejection below.
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.
Claim 56 is 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 56 recites the limitation "said individual" in step (a). There is insufficient antecedent basis for this limitation in the claim.
Dependent claims 57-60, 63, 65, 67 and 70-72 are also rejected under 112(b) as being dependent upon a rejection Claim 56.
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.
(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, 8, 9, 12, 13, 14, 56, 57, 58, 59, 60, 63 and 65 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WANG, WO 2015/112429 A1, submitted on the Information Disclosure Statement on 11 JUNE 2024, Foreign Patent Documents Cite No. 002.
Applicant’s invention is directed towards a method.
Regarding Claim 1, the WANG reference discloses a method for determining a likelihood that a subject has Alzheimer's Disease , abstract, [0128, 0162], Example 9, comprising:
(a) via immunoprecipitation, enriching a biological sample of said subject for proteins that are associated with said Alzheimer's Disease, [0010, 0049, 0082, 0086, 0150];
(b) directing a liquid medium comprising at least a subset of said proteins enriched in (a) to flow through a microfluidic device to separate individual proteins, [0046-0049], of said at least said subset of said proteins from one another, [0006, 0007, 0009, 0038-0042, 0049];
(c) via a targeted mass spectrometry (MS), [0035, 0088, 0089], selecting a preferred charge state of at least one of said individual proteins and generating signals assignable to said individual proteins or fragments thereof, [0007, 0012, 0021, 0034, 0136, 0137, 0152]; and
(d) determining, based at least in part on said signals, said likelihood that said subject is positive for said Alzheimer's Disease, [0128, 0162], Example 9.
Additional Disclosures Included are: Claim 8: wherein the method of claim 1, wherein said determining in (d) comprises determining a quantity for each of said individual proteins, [0036, 0045, 0081, 0121]. ; Claim 9: wherein the method of claim l, wherein said determining in (d) further comprises determining a ratio of at least two of said individual proteins, [0023, 0152, 0153]. ; Claim 12: wherein the method of claim 1, wherein said proteins comprise amyloid proteins, [0112]. ; Claim 13: wherein the method of claim 1, wherein said proteins comprise P- amyloid proteins, [0112]. ; Claim 14: wherein the method of claim 1, wherein said proteins comprise Ap38, APP669-711, Ap40, Ap42, or any combination thereof, [0112].
Applicant’s invention is directed towards a method.
Regarding Claim 56, the reference WANG discloses a method for determining a likelihood that a subject has Alzheimer's Disease, abstract, [0128, 0162], Example 9
(a) via immunoprecipitation, enriching a biological sample of said individual for proteins that are associated with said Alzheimer's Disease, [0010, 0049, 0082, 0086, 0150];
(b) directing a liquid medium comprising at least a subset of said proteins enriched in (a) to flow through a microfluidic device, [0046-0049], to separate individual proteins of said at least said subset of said proteins from one another, [0006, 0007, 0009, 0038-0042, 0049],
(c) via a targeted mass spectrometry (MS), [0035, 0088, 0089], selecting a preferred charge state of at least one of said individual proteins,; and generating been subjected to an enzymatic digestion process prior to (c), [0082], only in some cases the media may be used for protein enrichment and digestion, indicating that it is not assumed or inherent that enzymatic digestion occurs, and
(d) determining, based at least in part on said signals of (c), said likelihood that said subject is positive for said Alzheimer's Disease , [0128, 0162], Example 9.
13. Additional Disclosures Include are: Claim 57: wherein the method of claim 56, wherein said individual proteins are intact proteins, [0008]. ; Claim 58: wherein the method of claim 56, wherein said determining in (d) comprises determining a quantity of one or more of said individual proteins, [0009-0011, 0036]. ; Claim 59: wherein the method of claim 56, wherein said determining in (d) comprises determining a quantity for each of said individual proteins, [0009-0011, 0036, 0045, 0081]. ; Claim 60: wherein the method of claim 56, wherein said determining in (d) further comprises determining a ratio of at least two of said individual proteins, [0023, 0153]. ;Claim 63: wherein the method of claim 56, wherein said proteins comprise amyloid proteins, [0112]. ; and Claim 65: wherein the method of claim 56, wherein said proteins comprise Ap38, APP669-711, Ap40, Ap42, or any combination thereof, [0112].
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 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 15, 16, 66, 67, 70, 71 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over WANG, WO 2015/112429 A1, and further in view of KLAFKI, Int. J. Mol. Sci. 2020, 21, 6564; doi:10.3390/ijms21186564.
Regarding Claims 16 and 67, the WANG reference suggests the claimed invention, but is silent in regards to said determining of (d) further comprises determining a ratio of APP669-711 and Ap42.
The KLAFKI reference discloses a method of determining a likelihood that a subject has Alzheimer’s Disease, abstract, comprising : (a) via immunoprecipitation, enriching a biological sample of said subject for proteins that are associated with said Alzheimer’s Disease, abstract, page 9 of 25 and 17 of 25, and (c) via a targeted mass spectrometry (MS), selecting a preferred charge state of at least one of said individual proteins and generating signals assignable to said individual proteins or fragments thereof, page 18 of 25; and (d) determining, based at least in part on said signal, said likelihood that said subject is positive for said Alzheimer’s Disease, abstract, page 16-17 of 25; wherein said determining in (d) further comprises determining a ratio of APP669-711 and Ap42, abstract, page 6 of 25, 16 of 25.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the WANG reference with the determining step as taught by KLAFKI wherein said determining in (d) further comprises determining a ratio of APP669-711 and Ap42 to predict brain amyloid pathology with high accuracy or to differentiate Alzheimer’s dementia patients and subjects with dementia due to other reasons, page 2 of 25.
Regarding Claim 15, 66 and 70, the WANG reference suggests the claimed invention, but is silent in regards wherein said determining in (d) further comprises determining a ratio of Ap40 and Ap42 and is below a pre-determined threshold.
The KLAFKI reference discloses a method of determining a likelihood that a subject has Alzheimer’s Disease, abstract, comprising : (a) via immunoprecipitation, enriching a biological sample of said subject for proteins that are associated with said Alzheimer’s Disease, abstract, page 9 of 25 and 17 of 25, and (c) via a targeted mass spectrometry (MS), selecting a preferred charge state of at least one of said individual proteins and generating signals assignable to said individual proteins or fragments thereof, page 18 of 25; and (d) determining, based at least in part on said signal, said likelihood that said subject is positive for said Alzheimer’s Disease, abstract, page 16-17 of 25; wherein said determining in (d) further comprises determining a ratio of Ap40 and Ap42 and is below a pre-determined threshold, abstract, page 2 of 25, Figure 2, Table 1, Table 9, Figure 7, page 14-15 of 25.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the WANG reference with the determining step as taught by KLAFKI determining a ratio of Ap40 and Ap42 and is below a pre-determined threshold to predict brain amyloid pathology with high accuracy or to differentiate Alzheimer’s dementia patients and subjects with dementia due to other reasons, page 2 of 25.
Additional Disclosures Included are: Claim 71: wherein the method of claim 70, wherein said pre-determined threshold is between 0 and 0.1770, Table 9, Figure 7, page 14-15 of 25.; and Claim 72: wherein the method of claim 71, wherein said pre-determined threshold is about 0.1485, Table 9, Figure 7, page 14-15 of 25.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 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, LYLE ALEXANDER can be reached at (571) 272-1254. 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.
CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797