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 .
No Requirement for Restriction/Election has been mailed in this application. Claims 1-12 are pending in the application, and are examined upon their merits.
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 1-12 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 indefinite wherein it recites: “phosphorylated Tau protein (pTau; Thr181).” Parenthetical terms render the claim indefinite because it is unclear whether the limitation(s) in the parentheses are part of the claimed invention. In the instant claim it is unclear if the claims require phosphorylated Tau or Tau specifically phosphorylated at Threonine residue 181. This affects the scope of all depending claims, Claims 2-12.
Claim 2 is further indefinite wherein it recites the method further comprises at least one biomarker selected from the group comprising (iii) and (iv). The group is singular but there are two Markush lists. It is unclear if this claim requires at least one from all of those listed; or requires at least one from the list of (iii) and at least one from the list of (iv).
Claims 8, 10, and 12 are rejected because they recite “using” claimed elements without setting forth the definitive method steps for said use. MPEP 2173.05(q) states: “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). Claims 8-10 and 12 are analogous to the claims in Erlich: Claim 8 recites, “using one or more binding agents” and this affects the scope of dependent Claim 9; Claim 10, exactly like claims in Erlich, recites, “using an antibody”; and Claim 12 recites, “using an In Vitro kit”.
Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim.” Thus, Claims 8-10, and 12 are indefinite because the metes and bounds of “using” are not clearly set forth such that one would know what process steps would infringe the claimed method.
Claim 8 is further indefinite wherein it recites the limitation "wherein the biomarkers are detected by" in Claim 1. There is insufficient antecedent basis for this limitation in the claim since Claim 1 recites measuring and there is no mention of detecting.
Claim 9 is further indefinite wherein it recites binding agents are fixed on a solid support “including, but is not limited to, …”. This recitation is indefinite because it fails to clearly define the metes and bounds of the solid supports that are encompassed by the invention. A person would not know what supports infringe the method.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 depends from Claim 1, which recites measuring the expression levels of a panel of biomarkers in a biological sample, but Claim 8 now recites “wherein the biomarkers are detected by ….detecting at least one autoantibody specific for each biomarker”. Detecting an autoantibody specific for a biomarker provides no measurement of biomarker expression as required by Claim 1. Therefore, the method of Claim 8 is broader than the method of the parent claim and Claim 8 fails to further limit the subject matter of the claim upon which it depends, and fails to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea judicial exceptions without significantly more. The claim(s) recite(s) the abstract ideas of “diagnosis or prognosis”, “comparing” expression levels to reference levels, and “performing a statistical analysis” to obtain a score. Additionally, the claims recite a natural law/correlation/phenomenon; namely, that expression levels of the panel of endogenous biomarkers indicate a subject’s risk of developing a disease. Therefore, disease pathology is associated with altered biomarkers within the individual. These judicial exception(s) are not integrated into a practical application because the steps/elements recited in addition to the judicial exceptions (measuring the expression level of a panel of biomarkers) do not provide any of the considerations under MPEP 2106.05(a-c), (e) and (h) that demonstrate integration. Further, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements merely recite what was well-understood, routine and conventional in the art prior to the filing date of the application.
First, it is important to note that many of the biomarkers listed in the claims have synonyms within the art. For example, the proper gene abbreviation for Retinol Binding Protein 4 of the claims is RBP4 not RET4 and it is also called Plasma Retinol-Binding Protein, MCOPCB10 or RDCCAS (see attached Genecard search report).
The claim is directed to a method for the diagnosis or prognosis of Alzheimer' s disease (AD) in a subject, which is one of the statutory categories of invention (STEP 1:YES).
This claim recites diagnosis/prognosis and comparing, which belong in the enumerated grouping of abstract ideas defined as: “3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III)”. Further, the claims recite “performing a statistical analysis”, which is an enumerated grouping of abstract ideas are defined as: “1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I)”. Lastly, the claims further recite a natural correlation/phenomenon/law whereby risk of developing Alzheimer’s pathology is correlated with statistical scores that are 5 > 7.5 (see claim 1). The courts have identified the following concepts as examples of laws of nature or natural phenomena (see MPEP 2106.04(b)(I)): a correlation between the presence of myeloperoxidase in a bodily sample and cardiovascular disease risk, Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017); the existence of cell-free fetal DNA (cffDNA) in maternal blood, Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 1373, 115 USPQ2d 1152, 1153 (Fed. Cir. 2015); and, the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone, Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018). The case law cited is analogous to the claims at hand because the invention compares expression levels of endogenous markers to reference levels wherein a statistical score indicates a subject’s risk of developing the disease. Taken together, the claims recite at least one judicial exception (STEP 2A, Prong One: YES).
According to Step 2A, Prong Two, the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. This analysis turns to the additional elements recited within the claim (see MPEP 2106.04(d)). The additional elements in independent claim 1 are “a) measuring the expression levels of a panel of biomarkers in a biological sample from the subject …wherein the panel of biomarkers comprises: (i) Beta-amyloid 1-40 (A40); Beta-amyloid 1-42 (p3A42); Cell surface glycoprotein MUC18 (MUC18); Apolipoprotein C2 (APOC2); Apolipoprotein Al (APOA1); Albumin (ALBU); and retinol-binding protein 4 (RET4); and(ii) total Tau protein (tTau); phosphorylated Tau protein (pTau; Thr1 81); Apolipoprotein E (APOE); Clusterin (CLUS); SPARC (SPRC); Chitinase 3-like-1 (CH3L1/YKL40); and malate dehydrogenase 1 (MDHC)”. The “measuring” of instant Claim 1 is recited at a high level of generality so as to read upon any means of measuring the expression levels of biomarker, which reads on either protein or gene expression. Depending claims recite at least one additional biomarker (claim 2), which merely adds biomarker(s) to the observation of the natural phenomenon. Depending claims 5-6 recite a specific statistical analysis, namely, multiple of variation which refers to expressing the difference between data sets. It is a mathematical ratio that helps quantify how many units of spread separate two data distributions, and reads upon a mathematical calculation judicial exception (see Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (MPEP § 2106.04(a)(2), subsection I)). Claim 7 recites the biological sample is selected from a list comprising well-established medically relevant samples. While depending claims recite “an antibody specific for each of the biomarkers” they do not recite any specific, novel antibodies.
There are no additional elements that reflect any improvement within the technical field; there are no additional elements that apply the judicial exception(s) to a particular treatment or which utilize a particular machine; there are no additional elements that effect a transformation; and there are no additional elements that apply the judicial exception natural phenomenon in some other meaningful way beyond, generally, linking it to a field; namely, Alzheimer’s Disease. In this way the claims, as a whole, amount to nothing more than a drafting effort designed to monopolize the natural correlation itself. (STEP 2A, Prong Two: NO).
Regarding the method claimed, the specification states: “Methods for extracting or isolating proteins are known to those skilled in the art and are commercially available. The levels of the gene encoding the protein of interest can be quantified by means of any conventional method that allows detecting and quantifying said protein in a sample from a subject” (pg. 5). The disclosure further states: “Antibodies can be prepared using any of the methods known to one skilled in the art” (pg. 13). Therefore, in accordance with Berkheimer Memo III.A.1, the examiner has cited express statements in the specification indicates that the additional elements were sufficiently well-known, in the art at the time of filing, such that the specification does not need to describe the particulars thereof. In other words, the disclosure describes no new technology, but merely refers to techniques and elements that were known in the art at the time of filing.
Lastly, in accordance with Berkheimer Memo III.A.III. the examiner cites publications within the field of technical expertise, that demonstrate the well-understood, routine, conventional nature of the additional element(s). The following prior art teaches it was well established in the field of technical expertise that whole scale proteomics were used to identify biomarkers associated with Alzheimer’s Disease risk (Eleanor Drummond and Thomas Wisniewski. Chapter 3: Using Proteomics to Understand Alzheimer’s Disease Pathogenesis, in Wisniewski T, editor. Brisbane (AU): Codon Publications; 2019 Dec 20). The prior art teaches genomic studies have identified amyloid beta 1-40 levels, amyloid beta 1-42 levels, and Tau hyperphosphorylation as indicia of familial AD. The prior art further states: “Unbiased, mass-spectrometry-based proteomic studies of human AD brain tissue are essential to complement these genomic studies”. Unbiased, mass spectrometry provides levels for all proteins within a sample. Additionally, other prior art references teach the use of Elecsys assays to identify p-tau181 as a biomarker that is increased prominently preclinical AD (Suárez-Calvet et al., EMBO Mol Med (2020) 12:e12921). Therefore, the steps/elements recited in addition to the judicial exception were all well understood, routine, conventional activities in the field of lung injury prior to filing the application at hand (STEP 2B: NO).
The claimed steps/elements recited in addition to the judicial exception(s), alone or in combination, do not make an inventive contribution over the methods that were known in the art prior to filing, and they amount to mere observation of the natural phenomenon itself, by any means known, with the words “apply it” in order to append it to the field of AD risk.
For all of these reasons, Claims 1-12 are directed to the judicial exception without significantly more and are rejected.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675