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 Application/Amendments/Claims
Applicant’s response filed on 8/11/2025 has been considered. No claims have been amended. Claims 49-57 are the subject of the present office action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 62/479,663, PRO 62/584,381 and CON of 15/939,841 filed on 3/31/2017, 11/10/2017 and 3/29/2018, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 3/31/2017.
Claim Interpretation
According to applicant’s specification, amylospheroid refers to an aspherical aggregate of amyloid beta peptides which are known and commercially available (Spec, Definitions). Upon addition of amyloid beta peptides into an aqueous culturing medium, amyloid beta peptides will self-assemble to form amylospheroids as evidenced by Hoshi. By definition, an amylospheroid aggregate must consist of two or more amyloid beta peptides. Thus, 1000 nM of amyloid beta peptides would form 500 nM or less of amylospheroid particles assuming each amylospheroid is composed of two or more amyloid beta peptides.
Furthermore, with respect to the amylospheroid concentration ranges, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), see MPEP 2144.05.
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.
Claims 49, 51, 52, 53, 55, 56 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Chirila et al. US 2014/0248648, published 9/4/2014 (hereinafter Chirila, reference of record) as evidenced by Hoshi et al. US 2014/0350229, published 11/27/2014 (hereinafter Hoshi) in view of Alkon et al. US 2010/0021913, published 1/28/2010 (hereinafter Alkon, reference of record). This rejection is repeated for the same reasons of record as set forth in the Official action dated 2/12/2025. A response to applicant’s traversal is found below.
Claims 49 and 53: Chirila describes a diagnostic method for screening Alzheimer’s disease using peripheral tissues such as skin fibroblast cells (Chirila, abstract). Chirila states that while the methods herein describe fibroblast cells, “other cells such as blood cells” are also contemplated (Chirila, para 72). Chirila describes a diagnostic method wherein two populations of fibroblast cells are obtained from a subject with Alzheimer’s disease (AD) (Chirila, example 1 and claim 1). Chirila describes treating one population with amyloid beta peptides and culturing the two samples (amyloid beta treated and untreated) in a culture medium, thus reading on the first and second populations as described in claim 49 (Chirila, claim 1). Chirila describes comparing the results to a control known to have AD, thus reading on the first and second populations which both have amyloid beta peptides as described in claim 53 (Chirila, para 12 and claim 1 part e). Chirila describes culturing times ranging from 1 minutes to about 168 hours (Chirila, para 36 and claim 14). Chirila describes treatment with various concentrations of amyloid beta peptides and fragments including 1 µM (1000 nM) (Chirila, para 12, 26). As stated in the claim interpretation section, amylospheroid refers to an aspherical aggregate of amyloid beta peptides which are known and commercially available (Spec, Definitions). Upon addition of amyloid beta peptides into an aqueous culturing medium, amyloid beta peptides will self-assemble to form amylospheroids as evidenced by Hoshi (Hoshi, para 29, 31). By definition, an amylospheroid aggregate must consist of two or more amyloid beta peptides. Thus, 1000 nM of amyloid beta peptides would form 500 nM or less of amylospheroid particles assuming each amylospheroid is composed of two or more amyloid beta peptides. Chirila analyzes the morphology of the cultured cells relative to a control known to have Alzheimer’s disease, ultimately providing a diagnosis (Chirila, claim 1). Chirila describes other molecular measures which indicate Alzheimer’s disease specific deficits including protein kinase C (PKC), extracellular regulated kinase (ERK) and gene expression studies (Chirila, para 19). Although Chirila contemplates the use of blood cells, Chirila does not expressly describe the use of human B lymphocytes as described in independent claims 49 and 53.
Claims 51 and 55: Chirila describes culturing times ranging from 1 minute to about 168 hours (Chirila, para 36 and claim 14).
Claims 52, 56 and 57: Chirila describes treatment with various concentrations of amyloid beta peptides and fragments including 1 µM (1000 nM) (Chirila, para 12, 26). Chirila notes the aggregation of cells and amyloid beta peptides during the culturing process (Chirila, para 36 and claim 2). As stated in the claim interpretation section, amylospheroid refers to an aspherical aggregate of amyloid beta peptides which are known and commercially available (Spec, Definitions). Upon addition of amyloid beta peptides into an aqueous culturing medium, amyloid beta peptides will self-assemble to form amylospheroids as evidenced by Hoshi. By definition, an amylospheroid aggregate must consist of two or more amyloid beta peptides. Thus, 1000 nM of amyloid beta peptides would form 500 nM or less of amylospheroid particles assuming each amylospheroid is composed of two or more amyloid beta peptides. Furthermore, with respect to the amylospheroid concentration ranges, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), see MPEP 2144.05.
Claims 49 and 53: Alkon describes a similar diagnostic method for screening Alzheimer’s disease using peripheral tissues by examining changes in gene expression in the presence of a protein kinase C activator (Alkon, para 35-38 and claims 1 and 4). Alkon states that peripheral tissues such as lymphocytes or fibroblasts offer a way to identify gene expression profiles associated with inherited Alzheimer’s disease (Alkon, para 8). Furthermore, Alkon specifically lists lymphocytes as test cell embodiments (Alkon, para 44). It is argued that B lymphocytes are considered immediately envisagable from Alkon’s disclosure of lymphocytes as test cell embodiments given that there are only two known types of lymphocytes (B lymphocytes and T lymphocytes). A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure, such is the case presently, see MPEP § 2131.02.
It would have been prima facie obvious to one of ordinary skill in the art to use the lymphocytes described by Alkon in the diagnostic method for screening Alzheimer’s disease using peripheral tissues described by Chirila. Alkon specifically states that peripheral tissues such as lymphocytes or fibroblasts offer a way to identify gene expression profiles associated with inherited Alzheimer’s disease (Alkon, para 8). Therefore, one skilled in the art could have substituted the skin fibroblast cells described by Chirila for the lymphocytes described by Alkon using predictable means since both cell types share gene expression profiles associated with inherited Alzheimer’s disease. One would have been motivated to make this substitution given that lymphocytes can readily be extracted from a patient’s blood and constitute an alternative peripheral tissue for screening Alzheimer’s disease. One would have a reasonable expectation of success since the substitution of one cell type for another is routine in the art and Alkon provides express embodiments to both as peripheral tissues useful in screening for Alzheimer’s disease. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 49, 51, 52, 53, 55, 56 and 57 to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Applicant cites previous arguments from remarks made on 12/13/2023 and 10/16/2024 while maintaining that the Examiner has not shown how the Chirila and Alkon references when combined render the claimed invention obvious. Applicant previously argues that the findings of the present invention are unexpected and surprising in that a subject’s lymphocytes can be used in a PKC based test to diagnose Alzheimer’s disease. Applicant argues that Chirila is inapposite to the claimed methods since the disclosure of Chirila focuses on treating fibroblast skin cells with amyloid beta peptides for diagnosing Alzheimer’s disease. Applicant argues that although Chirila describes the examination of blood cells, does not specify which blood cells are cultured and examined. Applicant argues that there lacks motivation to examine B lymphocytes for diagnosing Alzheimer’s disease.
This argument has been fully considered but was not found persuasive. Although it is true that the majority of the disclosure of Chirila is focused on examining fibroblast cells, Chirila states that other cells such as blood cells are also contemplated (Chirila, para 72). One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references, see MPEP 2145. Motivation to combine the cited references comes from the fact that lymphocytes can readily be extracted from a patient’s blood and constitute an alternative peripheral tissue for screening Alzheimer’s disease. This is further supported by Alkon who examines peripheral tissues such as lymphocytes to identify gene expression profiles associated with inherited Alzheimer’s disease (Alkon, para 8). Therefore, one skilled in the art could have substituted the skin fibroblast cells described by Chirila for the lymphocytes described by Alkon using predictable means since both cell types share gene expression profiles associated with inherited Alzheimer’s disease.
Applicant further argues that Alkon is inapposite to the claimed invention and fails to cure the defects of Chirila. Applicant cites Khan to support a finding of teaching away. Applicant argues that one of ordinary skill would be dissuaded from practicing the claimed invention. Applicant points to para 38 from Kahn for support in showing that skin fibroblasts when treated with amylospheroid do not show a decrease in PKC and do not appear to show an increase in PKC either.
This argument has been fully considered but was not found persuasive since Chirila describes using protein kinase C (PKC) as a molecular measure which indicates Alzheimer’s disease in fibroblast cells. Although Khan may show that uncorrelated results from PKC measurements in fibroblast cells, one of ordinary skill would be motivated to examine PKC in other peripheral tissues such as lymphocytes since Alkon shows that these offer a way to identify gene expression profiles associated with inherited Alzheimer’s disease (Alkon, para 8). With respect to applicants’ arguments of the prior art teaching away, it is emphasized that teaching away requires the prior art to criticize, discredit, or otherwise discourage the claimed solution. From MPEP § 2141.02(VI): “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.” Since the prior art clearly does not do this, this argument is unconvincing.
Claims 50 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Chirila (supra) as evidenced by Hoshi (supra) and Alkon (supra) as applied to claims 49, 51, 52, 53, 55, 56 and 57 above in further view of Ibarreta et al. "Distinct pH homeostatic features in lymphoblasts from Alzheimer's disease patients." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 44.2 (1998): 216-222 (hereinafter Ibarreta, reference of record). This rejection is repeated for the same reasons of record as set forth in the Official action dated 2/12/2025. No specific traversal to the instant rejection can be found in applicants remarks.
A description of Chirila, Hoshi and Alkon can be found above. Neither Chirila nor Alkon describe the use of immortalized B lymphocytes.
Claims 50 and 54: However, reliable methods exist in the art to immortalize B lymphocytes. For example, Ibarreta describes the use of the Epstein-Barr virus to immortalize B lymphocytes in a study examining the intracellular pH of cells from Alzheimer’s disease patients (Ibarreta, abstract and intro para 3). Ibarreta summarizes the important role B lymphocytes play in Alzheimer’s disease (Ibarreta, intro).
It would have been prima facie obvious to one of ordinary skill in the art to use the immortalize B lymphocytes described by Ibarreta in the diagnostic method for screening Alzheimer’s disease using peripheral tissues described by Chirila in view of Alkon. Immortalized cell lines have been manipulated to proliferate indefinitely and can be cultured for long periods of time. Therefore, one skilled in the art could have substituted the lymphocytes described by Alkon for the more robust immortalize B lymphocytes described by Ibarreta using predictable means. One would have been motivated to make this substitution given that immortalize B lymphocytes could be cultured for longer periods of time given the limitations of claims 45 and 48 requiring more than six hours of culturing. One would have a reasonable expectation of success given that there are predictable means of immortalizing B lymphocytes as shown by Ibarreta. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims 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 extension fee 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 ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 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, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634