DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 7-8 and 15-16 are pending in this application.
Applicant’s amendment to the specification filed 07/03/2025 is acknowledged.
Applicant’s remarks filed on 07/03/2025 in response to the non-final rejection mailed on 01/03/2025 is acknowledged and has been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, claim 7, drawn to the technical feature of a method for diagnosing Alzheimer's disease in a symptomatic human subject comprising measuring the protein amount of the subject's skin fibroblasts under protein amount-measuring conditions, whereby the subject is afflicted with Alzheimer's disease if the protein amount of the subject's skin fibroblasts is lower, by at least one standard deviation, than the average protein amount of non-Alzheimer's disease dementia skin fibroblasts measured under the same protein amount-measuring conditions,
elected without traverse in the reply filed 09/12/2024.
Claims 8 and 15-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/12/2024.
Claim 7 is being examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 02/13/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Objections to Specification
The objections to the specification are withdrawn in view of the amendments to address the use of trademarks.
Claim Rejections - 35 USC § 112(b)
The rejection of claim 7 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention is withdrawn upon further consideration. The phrase “protein amount-measuring conditions” is broadly and reasonably interpreted to encompass any conditions under which protein amount can be measured.
Claim Rejections - 35 USC § 102
Claim 7 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khan et al. (J Alz Dis, 2015, 43:491; cited on the Form PTO-892 mailed 01/02/2025; herein referred to as Khan).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 7 is drawn to a method for diagnosing Alzheimer’s disease (AD) in a symptomatic human subject comprising measuring the protein amount of the subject’s skin fibroblasts under protein amount-measuring conditions, whereby the subject is afflicted with AD if the protein amount of the subject’s skin fibroblasts is lower, by at least one standard deviation, than the average protein amount of non-AD dementia skin fibroblasts measured under the same protein amount-measuring conditions.
Khan discusses protein kinase C ε (PKCε) deficits in AD skin fibroblasts [title], and describes that the protein PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD [abstract].
Regarding claim 7, Khan teaches a method of isolating skin fibroblasts from patients with AD and patients with non-AD dementia [p 492, col 2, para 2], quantifying the amounts of PKCε via immunoblot [p 493, col 2, para 2], and performing statistical analysis on results [p 498, col 1, para 2], wherein lower levels of PKCε were found in AD skin fibroblasts [p 500, col 1, para 1, and Figure 4, wherein non-AD dementia samples are represented as HD]. Khan additionally teaches that average ratio of PKCε to β-tubulin control in immunoblots from skin fibroblasts was 1.040 ± 0.288 (SEM) in non-AD dementia samples compared to 0.501 ± 0.021 (SEM) in AD samples [p 501, col 1, para 2], wherein SEM is understood to be standard error measurement, and wherein the difference in samples is considered to correspond to at least one standard deviation as recited in the claim.
For these reasons, Khan anticipates claims 7.
Response to Remarks: beginning p 5 of Applicant’s response to rejections under 35 USC 102; Applicant in summary contends Khan does not disclose measuring the total amount of protein in a subject’s skin fibroblasts, and therefore claim 7 is novel over Khan.
Applicant’s remarks are considered and found not convincing. Given a broadest reasonable interpretation, the phrase “measuring the protein amount of the subject’s skin fibroblasts” is interpreted as encompassing measuring the amount of a single protein, the amount of a subset of proteins, or the amount of total proteins present in a subject’s skin fibroblasts. While Khan does not disclose measuring the total amount of protein in a subject’s skin fibroblasts as Applicant states, claim 7 does not recite measuring the total protein amount of skin fibroblasts and thus, the measurement of the total amount of protein in a subject’s skin fibroblasts is not a feature of claim 7. Put another way, the claim does not recite the limitation “measuring the total amount of protein in a subject’s skin fibroblasts.” Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See MPEP 2111.01.II.
Double Patenting
A. Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 5,976,816 (cited on the Form PTO-892 mailed 01/02/2025; herein “patent”) in view of Khan.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 7 is drawn to a method for diagnosing Alzheimer’s disease (AD) in a symptomatic human subject comprising measuring the protein amount of the subject’s skin fibroblasts under protein amount-measuring conditions, whereby the subject is afflicted with AD if the protein amount of the subject’s skin fibroblasts is lower, by at least one standard deviation, than the average protein amount of non-AD dementia skin fibroblasts measured under the same protein amount-measuring conditions.
Regarding instant claim 7, claim 1 of the patent recites a method of diagnosing AD comprising comparing levels of a protein Cp20 from a patient and comparing them to a control, wherein the decrease in Cp20 is indicative of AD, and claim 3 of the patent recites the sample is derived from the patient’s fibroblast cells.
The claims of the patent do not recite the comparison to a non-AD dementia control, or the measurement in skin fibroblasts.
Khan discusses protein kinase C ε (PKCε) deficits in AD skin fibroblasts [title], and describes that the protein PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD [abstract].
Regarding instant claim 7, Khan discloses a method of isolating skin fibroblasts from patients with AD and patients with non-AD dementia [p 492, col 2, para 2], quantifying the amounts of PKCε via immunoblot [p 493, col 2, para 2], and performing statistical analysis on results [p 498, col 1, para 2], wherein lower levels of PKCε were found in AD skin fibroblasts [p 500, col 1, para 1, and Figure 4, wherein non-AD dementia samples are represented as HD]. Khan additionally discloses that average ratio of PKCε to β-tubulin control in immunoblots from skin fibroblasts was 1.040 ± 0.288 (SEM) in non-AD dementia samples compared to 0.501 ± 0.021 (SEM) in AD samples [p 501, col 1, para 2], wherein SEM is understood to be standard error measurement, and wherein the difference in samples is considered to correspond to at least one standard deviation as recited in the claim.
In view of Khan, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts from AD patients and controls from non-AD dementia patients as disclosed by Khan, to arrive at the claimed invention, since the combination of known prior art elements according to known methods results in a predictable result. One of ordinary skill in the art would have been motivated to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts, because Khan discloses PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD. One of ordinary skill in the art would have had a reasonable expectation of success because both the patent and Khan discuss methods for diagnosing AD by comparing protein levels in AD patients and controls.
B. Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 7,595,167 (cited on the Form PTO-892 mailed 01/02/2025; herein “patent”) in view of Khan.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 7 is drawn to a method for diagnosing Alzheimer’s disease (AD) in a symptomatic human subject comprising measuring the protein amount of the subject’s skin fibroblasts under protein amount-measuring conditions, whereby the subject is afflicted with AD if the protein amount of the subject’s skin fibroblasts is lower, by at least one standard deviation, than the average protein amount of non-AD dementia skin fibroblasts measured under the same protein amount-measuring conditions.
Regarding instant claim 7, claim 1 of the patent recites a method of diagnosing AD comprising comparing levels of phosphorylated MAP kinase proteins from a patient, and claim 4 of the patent recites the sample is derived from the patient’s skin fibroblast cells.
The claims of the patent do not recite the comparison to a non-AD dementia control, or that decreased protein in the patient’s sample indicates AD.
Khan discusses protein kinase C ε (PKCε) deficits in AD skin fibroblasts [title], and describes that the protein PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD [abstract].
Regarding instant claim 7, Khan discloses a method of isolating skin fibroblasts from patients with AD and patients with non-AD dementia [p 492, col 2, para 2], quantifying the amounts of PKCε via immunoblot [p 493, col 2, para 2], and performing statistical analysis on results [p 498, col 1, para 2], wherein lower levels of PKCε were found in AD skin fibroblasts [p 500, col 1, para 1, and Figure 4, wherein non-AD dementia samples are represented as HD]. Khan additionally discloses that average ratio of PKCε to β-tubulin control in immunoblots from skin fibroblasts was 1.040 ± 0.288 (SEM) in non-AD dementia samples compared to 0.501 ± 0.021 (SEM) in AD samples [p 501, col 1, para 2], wherein SEM is understood to be standard error measurement, and wherein the difference in samples is considered to correspond to at least one standard deviation as recited in the claim.
In view of Khan, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts from AD patients and controls from non-AD dementia patients as disclosed by Khan, to arrive at the claimed invention, since the combination of known prior art elements according to known methods results in a predictable result. One of ordinary skill in the art would have been motivated to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts, because Khan discloses PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD. One of ordinary skill in the art would have had a reasonable expectation of success because both the patent and Khan discuss methods for diagnosing AD by determining protein levels in AD patient skin fibroblast samples.
C. Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. 9,188,595 (cited on the Form PTO-892 mailed 01/02/2025; herein “patent”) in view of Khan.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 7 is drawn to a method for diagnosing Alzheimer’s disease (AD) in a symptomatic human subject comprising measuring the protein amount of the subject’s skin fibroblasts under protein amount-measuring conditions, whereby the subject is afflicted with AD if the protein amount of the subject’s skin fibroblasts is lower, by at least one standard deviation, than the average protein amount of non-AD dementia skin fibroblasts measured under the same protein amount-measuring conditions.
Regarding instant claim 7, claim 1 of the patent recites a method of diagnosing AD comprising comparing levels of phosphorylated MAP kinase proteins from a patient to those from a non-AD patient, and claim 6 of the patent recites the sample is derived from the patient’s skin fibroblast cells.
The claims of the patent do not recite the comparison to a non-AD dementia control, or that decreased protein in the patient’s sample indicates AD.
Khan discusses protein kinase C ε (PKCε) deficits in AD skin fibroblasts [title], and describes that the protein PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD [abstract].
Regarding instant claim 7, Khan discloses a method of isolating skin fibroblasts from patients with AD and patients with non-AD dementia [p 492, col 2, para 2], quantifying the amounts of PKCε via immunoblot [p 493, col 2, para 2], and performing statistical analysis on results [p 498, col 1, para 2], wherein lower levels of PKCε were found in AD skin fibroblasts [p 500, col 1, para 1, and Figure 4, wherein non-AD dementia samples are represented as HD]. Khan additionally discloses that average ratio of PKCε to β-tubulin control in immunoblots from skin fibroblasts was 1.040 ± 0.288 (SEM) in non-AD dementia samples compared to 0.501 ± 0.021 (SEM) in AD samples [p 501, col 1, para 2], wherein SEM is understood to be standard error measurement, and wherein the difference in samples is considered to correspond to at least one standard deviation as recited in the claim.
In view of Khan, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts from AD patients and controls from non-AD dementia patients as disclosed by Khan, to arrive at the claimed invention, since the combination of known prior art elements according to known methods results in a predictable result. One of ordinary skill in the art would have been motivated to modify the method of the patent by comparing the levels of PKCε in skin fibroblasts, because Khan discloses PKCε, which prevents synaptotoxic amyloid-β elevation, is found at decreased levels in skin fibroblasts from patients with AD. One of ordinary skill in the art would have had a reasonable expectation of success because both the patent and Khan discuss methods for diagnosing AD by determining protein levels in AD patient skin fibroblast samples.
Response to Remarks: beginning p 5 of Applicant’s response to double patenting rejections; Applicant will consider filing a terminal disclosure once the claims are otherwise allowable.
Applicant’s remarks are acknowledged, and the rejections are maintained.
Conclusion
Status of the Application:
Claims 7-8 and 15-16 are pending.
Claims 8 and 15-16 are withdrawn.
Claims 7 is rejected.
No claim is in condition for allowance.
THIS ACTION IS MADE FINAL. 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 JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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, Manjunath Rao can be reached at (571) 272-0939. 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.
/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656