DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending.
Specification
The disclosure is objected to because of the following informalities: The Brief Description of the Drawings do not refer to Figs. 12D-F.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on paragraph 174. 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.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The claims recite “judicial exceptions” as a limiting element or step without reciting additional elements/steps that integrate the judicial exceptions into the claimed inventions such that the judicial exceptions are practically applied, and are sufficient to ensure that the claims amount to significantly more than the judicial exceptions themselves. In the instant case, the “judicial exceptions” include the natural phenomenon, the level of amyloid precursor protein (APP) specific CD8+ T cells and the detection of Alzheimer’s disease. In addition, the claims include the abstract ideas, comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample and “determining that the subject has an Alzheimer’s disease or a predisposition to Alzheimer’s disease based on altered levels of expression” which are not eligible for patent protection without significantly more recited in the claims.
A claim that focuses on use of judicial exceptions must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The PTO’s revised guidance on the application of § 101. (USPTO's January 7, 2019, Memorandum, 2019 Revised Patent Subject Matter Eligibility Guidance indicates that we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract
ideas (i.e., mathematical concepts, certain methods of organizing
human activity such as a fundamental economic practice, or mental
processes); and
(2) additional elements that integrate the judicial exception into a
practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that
exception into a practical application, do we then look to whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not
"well-understood, routine, conventional" in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
The present claims are directed to judicial exceptions? The claims recite judicial exceptions as limiting elements, the natural phenomenon, the level of amyloid precursor protein (APP) specific CD8+ T cells and the presence of Alzheimer’s disease. In addition the claims recite abstract ideas, “comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample” and “determining that the subject has an Alzheimer’s disease or a predisposition to Alzheimer’s disease based on altered levels of expression”. These limitations could be done by merely reviewing the data mentally comparing and mentally determining that the subject has an increased likelihood of Alzheimer’s disease. In addition, these limitations encompasses mathematical equations or graphs which could be used to identify, predict and select. However, these limitation would be considered to be abstract ideas and would not been given patentable weight. The Court has pointed out that the basic mathematical equation, like a law of nature, was not patentable.
The Court in Diehr, Flook and Alice Corporation have pointed out that the basic mathematical equation, like a law of nature, was not patentable. The Court in Diehr, found that there were other steps added to the formula that in terms of patent law’s objectives had significance—they transformed the process into an inventive application of the formula. In the present claims there are active method steps that transform the process into a practical application of the determining step but the treatment step is not required if there is no difference in the level of expression of the amyloid precursor protein (APP) specific CD8+ T cells between the reference sample and the subject sample. The claims encompass embodiments in which there is no treatment, ie in which there is no difference in the level of expression of the amyloid precursor protein (APP) specific CD8+ T cells between the reference sample and the subject sample.
The next step is to determine whether the claim as a whole adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field. the active method step of “assaying the sample to determine the level of amyloid precursor protein (APP)specific CD8+ T cells by quantitating the number of APP-specific CD8+ T cells in the sample sets forth well-understood, routine and conventional activity engaged in by scientists at the time the application was filed and are the activities that a scientist would have relied upon to achieve the goals of the invention. Monsonegro et al (J Clin Invest, 112:415-422, 2003, IDS) disclose measuring T cells in peripheral blood that responded to the immunodominant epitope of the amyloid β protein in patients with Alzheimer’s disease (page 417, 1st column to page 420 1st column; Figure 3). Speciale et al (Neurobio Aging, 28:1163-1169, 2007) disclose measuring activated CD8+ cells in the peripheral blood of patients with Alzheimer’s disease (page 1166; page 1167, 2nd column; Table 3).
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
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.
Claims 1-20 are rejected 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims recite obtaining a reference tissue sample and “comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample”. It is not clear how this same reference sample can be used to detect Alzheimer's disease, detect a predisposition to Alzheimer's disease in a subject and determine the prognosis of a subject with Alzheimer's disease.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for detecting a subject with Alzheimer's disease comprising comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample, does not reasonably provide enablement for methods for detecting a predisposition or method for detecting a prognosis of a subject with Alzheimer's disease comprising comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The claims are drawn to a method for detecting Alzheimer's disease or a detecting a predisposition to Alzheimer's disease in a subject, the method comprising:
(a) obtaining a tissue sample from the subject;
(b) obtaining a reference tissue sample;
(c) comparing levels of expression of amyloid precursor protein (APP) specific
CD8+ T cells in the reference sample and the subject sample;
(d) determining the subject has Alzheimer's disease or a predisposition to
Alzheimer's disease based on altered levels of expression
The specification discloses that decreased KLRG1 + APP(471-479)-specific CD8 T cells in blood distinguished Alzheimer's disease from normal aging patients with less overlap than another promising blood-based biomarker for Alzheimer's disease in development, plasma levels of P-Tau217 (Example 9). The specification disclose that hiT-bearing mouse pathology was accompanied by plaque and neurofibrillary deposits, and a pattern of hippocampus- to amygdala-dependent cognitive deficits which are typical of Alzheimer's disease (Example 8). However, the specification does not disclose any examples demonstrating that there is a correlation between amyloid precursor protein (APP) specific CD8+ T cells and the predisposition or prognosis of Alzheimer's disease.
Tockman et al (Cancer Res 52:2711s-2718s, 1992) teach considerations necessary in bringing a cancer biomarker to successful clinical application. Although the reference is drawn to biomarkers for early Alzheimer’s detection, the basic principles taught are clearly applicable to other disorders and associated markers such as expression levels of amyloid precursor protein (APP) specific CD8+ T cells. Tockman et al teach that prior to the successful application of newly described markers, research must validate the markers against acknowledged disease end points, establish quantitative criteria for marker presence/absence and confirm marker predictive value in prospective population trials (see abstract). Early stage markers have clear biological plausibility as biomarkers of and if validated can be used for population screening (p. 2713s, col 1). The reference further teaches that once selected, the sensitivity and specificity of the biomarker must be validated to a known (histology/cytology-confirmed) outcome. The essential element of the validation of an early detection marker is the ability to test the marker on clinical material obtained from subjects monitored in advance of clinical cancer and link those marker results with subsequent histological confirmation of disease. This irrefutable link between antecedent marker and subsequent acknowledged disease is the essence of a valid intermediate end point marker (p. 2714, see Biomarker Validation against Acknowledged Disease End Points). Clearly, prior to the successful application of newly described markers, markers must be validated against acknowledged disease end points and the marker predictive value must be confirmed in prospective population trials (p. 2716s, col 2).
The art does not disclose any evidence that predisposition and prognosis of Alzheimer’s can be determined using subsets of T cells.
One cannot extrapolate the teaching of the specification to the enablement of the claims because the specification does not provide examples or guidance for detecting a predisposition or method for detecting a prognosis of a subject with Alzheimer's disease by comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample. The specification only demonstrates detecting Alzheimer's disease by comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample. There are no examples demonstrating detecting a predisposition or method for detecting a prognosis of a subject with Alzheimer's disease by comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample. The specification does not provide a nexus between the expression of amyloid precursor protein (APP) specific CD8+ T cells and the predisposition or prognosis of Alzheimer's disease.
MPEP 2164.03 states that
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention.
MPEP 2164.03 further states that
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability. …
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.
MPEP 2164.08(b) states that
The presence of inoperative embodiments within the scope of a claim does not necessarily render a claim nonenabled. The standard is whether a skilled person could determine which embodiments that were conceived, but not yet made, would be inoperative or operative with expenditure of no more effort than is normally required in the art. Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984) (prophetic examples do not make the disclosure nonenabling).
Although, typically, inoperative embodiments are excluded by language in a claim (e.g., preamble), the scope of the claim may still not be enabled where undue experimentation is involved in determining those embodiments that are operable. A disclosure of a large number of operable embodiments and the identification of a single inoperative embodiment did not render a claim broader than the enabled scope because undue experimentation was not involved in determining those embodiments that were operable. In re Angstadt, 537 F.2d 498, 502-503, 190 USPQ 214, 218 (CCPA 1976). However, claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.
Given the disclosure of the specification and the teaching in the art that indicates the considerations necessary in bringing a cancer biomarker to successful clinical application, one skilled in the art could not predictably detect the predisposition or prognosis of a subject with Alzheimer's disease by comparing levels of expression of amyloid precursor protein (APP) specific CD8+ T cells in the reference sample and the subject sample.
Therefore, in view of the breadth of the claims, lack of guidance in the specification, the absence of working examples, and the state of the art, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,567,078. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-19 of U.S. Patent No. 11,567,078 are drawn to method for determining the likelihood of late onset Alzheimer's disease (LOAD) in a subject comprising:
(i) obtaining a sample from the subject;
(ii) assaying the sample to determine the level of amyloid precursor protein (APP) specific CD8+ T cells; and
(iii) determining that the subject has an increased likelihood of LOAD if the level of the APP-specific CD8+ T cells is higher relative to a reference sample, and
(iv) treating the subject with an immunomodulating agent
when the subject has an increased likelihood of LOAD.
LOAD would be a considered to be a species of Alzheimer’s disease.
Summary
No claims allowed.
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646