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 .
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.
DETAILED ACTION
This action is in response to claim amendments filed 6/29/26. Claims 13-23 are pending. Applicant’s election without traverse of Group II remains in effect. The species election for the detection agent is withdrawn.
Claims 13 and 15-21 are withdrawn. Claims 14 and 22-23 are under examination.
Withdrawn Rejections
The objections to the drawings are withdrawn in light of the new drawings.
The claim objection is withdrawn in light of the amendment.
The claims no longer recite the word “agent”.
The rejections under §112b are withdrawn in light of the amendments.
The rejections under §102 and §103 are withdrawn in light of the amendments.
The double patenting rejection over 18548023 is withdrawn. The current amendments add additional steps, such as detecting CD106 in combination with another biomarker. The co-pending application requires diagnosis of diabetes by detecting abnormal cells (claim 21). The phrase “abnormal cells” does not appear to be defined by the specification. In reading the specification to determine how such a term might be defined, it does not appear to include detecting CD106 (see e.g., claim 6 in ‘023, where the cells do not express CD106). So, while the instant claims are specific and may anticipate/make obvious the co-pending claims in 18/548023, the reverse does not appear to be true.
Maintained Rejections and New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
Claims 14 and 22-23 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 certain combinations demonstrated as increased in a particular species in diabetes, does not reasonably provide enablement for the breadth of biomarkers claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The nature of the invention is in detecting certain combinations of biomarkers to diagnose a subject as having diabetes mellitus (DM), having a diabetic complication, a risk of developing DM, or a risk of developing a diabetic complication. Note that the broadest reasonable interpretation of this combination of diagnoses is that the method allows for determining the subject has at least one of these conditions without necessarily determining which of the four the subject has. This is because a single obtained value is claimed for all four of these diagnoses and the instant specification does not provide information regarding a differential diagnosis between the four, e.g., how this value differentiates “having diabetes” from “having a diabetic complication”.
The breadth is that in either mice or humans, the same biomarkers can be evaluated from HSCs to make this determination. While skill in the art is high, predictability is low. The guidance in the instant specification coupled with the knowledge in the art is insufficient to use the instant method as broadly as it is claimed without undue experimentation.
For example, claim 14 requires the HSCs obtained from humans to be CD34+ but no such requirement exists for the murine HSCs. The instant specification states “CD34 represents a feature of a stem cell in humans” (p.82) with no similar statement for mice. The art, on the other hand, recognizes that CD34 is not a feature of adult murine cells. Ito (form 892) teaches adult HSCs are CD34- while fetal cells are CD34+ (abstract). Ito teaches this transition is a developmental change that occurs over time (abstract).
The specification does not appear to offer data regarding the expected amount of CD34 in adult murine HSCs while the art teaches this value is zero (Ito figure 2). Yet, the claims encompass detecting CD34 in mice to make the relevant determinations. An increased value of CD34 in murine HSCs might indicate diabetes or it might indicate a less mature population of HSCs. Where Applicant has not actually compared the values in a diabetic vs non-diabetic subject in a particular species for a particular combination of biomarkers, others are left to determine the validity of Applicant’s hypothesis, which is undue experimentation. The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
"[T]o be enabling, the specification.., must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" Wright, 999 F.2d at 1561, 27 USPQ2d at 1513 (emphasis added), quoted in Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997). Thus, "there must be sufficient disclosure, either through illustrative examples or terminology, to teach those of ordinary skill how to make and how to use the invention as broadly as it is claimed." In re Vaeck, 947 F.2d 488, 496 & n. 23, 20 USPQ2d 1438, 1445 & n. 23 (Fed. Cir. 1991), quoted in Enzo Biochem, Inc. v. Calgene, lnc., 188 F.3d 1362, 1372, 52 USPQ2d 1129, 1138 (Fed. Cir. 1999).
"Patent protection is granted in return for an enabling disclosure..., not for vague intimations of general ideas that may or may not be workable." Genentech, 108 F.3d at 1365, 42 USPQ2d at 1005. "Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public [skilled in the art] to understand and carry out the invention." Id. at 1366, 42 USPQ2d at 1005 (emphasis added).
Therefore, claims 14 and 22-23 are not enabled for their full scope.
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 14 and 22-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A prong 1. Claims 14 and 22-23 are methods and fall within the statutory category of a process.
Step 2A, prong 1: Prong 1 requires the Examiner to evaluate whether the claim recites a judicial exception and, if so, proceed to prong 2. In this case, the claim detects and compares biomarkers and recites “diagnosing the subject as having diabetes…when” and then reciting the observed conditions in which such a diagnosis is made. This is the recitation of a judicial exception (natural correlation; observation of a natural phenomenon).
Step 2A, prong 2: Prong 2 requires the Examiner to evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception and, if not, proceed to step 2B. In order to integrate the recited judicial exception into a practical application, the claim will apply, rely on, or use the judicial exception that imposes a meaningful limit such that the claim is more than a drafting effort to monopolize the judicial exception. Examiners evaluate integration by identifying additional elements in the claim beyond the judicial exception and evaluating those elements individually and in combination to determine whether they integrate the exception into a practical application. Examples that have been found by the Courts in which the exception was not integrated into a practical application include:
Mere instructions to implement an abstract idea on a computer
Adding generic instructions that the judicial exception should be used ("apply it")
Adding insignificant extrasolution activity to the exception ("mere data gathering")
Generally linking the use of the exception to a particular technological environment or field of use
In this case, there are no steps after the mental conclusion of a diagnosis and so there is nothing after the observation to integrate the exception. The steps prior to the mental conclusion are the data gathering steps necessary to observe the phenomenon and so represent insignificant extrasolution activity. Obtaining the sample comprising the relevant cells to be observed, detecting the relevant biomarker in those cells, and comparing these values are all steps required to gather the data for making the conclusion. Further, these claims are recited at a high level of generality, e.g., detect the biomarker by any means, informing others regarding in which cells the phenomenon can be observed, etc. The claim as a whole amounts to directions to observe a certain property (biomarker levels on certain cells from certain subjects) and informing others as to the relevance of that observation. The step of diagnosing is a mental conclusion performed once the relevant information has been gathered. It is either part of the judicial exception itself or else recited at such a high level of generality as to be no more than instructions to “apply it” as the phenomenon itself is the correlation between these biomarkers and diabetes mellitus.
For claim 22, this claim is directed to generic assays (immunoassay, gene expression analysis). This is recited at a high level of generality and is part of the “mere data gathering” step of the observation.
For claim 23, antibodies, probes, and primers are generic molecules that encompass essentially no more than instructions to detect the biomarkers. Further, this is part of the “mere data gathering” step.
Step 2B: Where a claim does not integrate the exception, a claim may nevertheless be patent eligible, for example where additional elements are “significantly more” than the exception such that the additional elements were unconventional in combination. Considerations include whether or not the claim adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; or simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present. In this case, the claims are recited at such a broad, generic level so as to encompass essentially any known way of observing the biomarkers. The Courts have recognized that “determining the level of a biomarker in blood by any means” is a well-known, routine, and conventional activity (MPEP §2106). The “detecting” in claim 14 encompasses any possible means for doing so and so is similarly recognized as conventional activity. Claims 22 and 23 encompass using probes or primers to detect genetic expression, which is also recognized by the Court as well-known (MPEP §2106 “detecting DNA or enzymes in a sample”). There is no limitations regarding how the sample is obtained and so encompasses all well-known methods of doing so. The “comparing” step encompasses comparing two numbers, which is a well-known, routine, and conventional human activity. This is also supported by the art. See:
US20020006621 (form 892) teaches making a diagnosis by obtaining a biological sample (peripheral blood), using DNA probes to detect gene expression (a probe is used; a gene expression analysis is used), and comparing values to make a diagnosis. This includes detecting CD34 in HSCs. See for example claims 34 and 41 as well as paragraph 123.
US20030104419 (form 892) teaches diagnosing a disease by providing a test cell population (biological sample) from a subject (which must necessarily have been obtained to be provided), measuring (detecting) nucleic acids and comparing the gene expression to a reference cell. See for example claim 14.
US20140038901 (form 892) teaches obtaining biological samples, measuring (detecting) biomarkers, and comparing those biomarkers to a reference level. See, e.g., claims 1, 6, 15.
Considering the claim as a whole, there are no steps beyond the judicial exception itself that were unconventional.
Therefore, claims 14, 22, and 23 are patent ineligible.
Response to Arguments
Applicant's arguments filed 6/29/26 have been fully considered but they are not persuasive.
Regarding the double patenting rejection, Applicant argues an intent to file a terminal disclaimer. This is not a complete response to a double patenting rejection. Nonstatutory double patenting rejections, including provisional ODP rejections, are not held in abeyance (MPEP §804(I)(B)(1)). Nevertheless, the double patenting rejection is withdrawn for other reasons (see above).
Regarding the §101 rejection, Applicant argues the claims are directed to a specific laboratory-based method for diagnosing diabetes. This is not persuasive because the laboratory-based method is not specific. Rather it is recited at a high level of generality including obtaining a sample (by any means), detecting a biomarker (by any means) and comparing obtained values. Further, these are part of the extrasolution data gathering step.
Applicant argues the method requires obtaining a biological sample comprising HSCs. The relationship between the biomarkers on HSCs and the disease is part of the judicial exception and so obtaining the necessary sample is extrasolution activity and well-known as above. Applicant argues the method requires identifying HSCs having a specified phenotype. This is not persuasive because this is not claimed. While the claim requires the cells to have a specific phenotype, no identification of that phenotype is claimed. The method step is met so long as those cells exist in the sample whether or not they’ve been identified. Applicant argues the method requires detecting expression of multiple biomarkers and comparing these levels to other levels. The correlation between the levels of these markers in disease vs non-disease state is part of the judicial exception, while the “detecting” is recited at a high level of generality and is part of the extrasolution data gathering step. Applicant argues the claim requires the step of “diagnosing”. This is either part of the judicial exception itself or simply instructions to “apply it” as discussed above.
Applicant argues the above amounts to a practical application because the method generates diagnostically useful information. This is not persuasive because generating the information, e.g., informing others about the natural correlation, is the judicial exception. There is no integration because after generating the information, the only step is “diagnose”, which is essentially just “apply it” since the natural phenomenon is the correlation between the biomarkers on HSCs and the disease.
Conclusion
No prior art rejection is made. TNF-α in HSCs was already known to be associated with diabetes (Katagi; form 892). However, all examined claims require measuring expression of CD106 in these cells. It was known that CD106 (VCAM) could be detected on HSCs but was generally associated with healthy HSCs (Pinho; form 892). Also of note is Tsukamoto (IDS 4/15/22 citation 7) which teaches increased VCAM on inflamed islets (abstract). Pertseva (IDS 4/15/22 citation 6) teaches increased VCAM in blood but not “in the HSCs” as instantly claimed.
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 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 ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/Primary Examiner, Art Unit 1675
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