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
Election/Restrictions
Claims 1-2, 4-7, 10-12, and 16-28 are pending.
Applicant’s election without traverse of Group I (comparing IGFBP7 levels to assess previous silent infarcts) and the species of polypeptide in the reply filed on 3/16/26 is acknowledged.
Claims 4-6, 18-19, and 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6/16/26. Note that there was a typo in the original restriction indicating claims 21, 23 and 24 were part of group I; however, these claims depend from claim 4 which defines groups III and IV.
Applicant has amended the Markush group in claim 16 and presented other options as new claims 27 and 28. The species election is withdrawn.
Claims 1-2, 7, 10-12, 16-17, 20, and 27-28 are under examination.
Claim Interpretation
Claim 7 refers to “the silent infarcts”. Claim 1 includes only one silent infarct. By referring to the plural, claim 7 necessarily also excludes the subject having experienced only one infarct.
Claim Rejections - 35 USC § 112
Claim 12 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “the subject is human” with “the sample is blood, serum, plasma, and/or tissue” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The state of “being human” is not an alternative to a sample “being blood”. Aspects of the subject are not in the same class as the aspects of the sample taken from that subject. While a human contains blood, serum, etc., the claim is not setting these two alternatives forth for the same use. The subject is being analyzed for experience of a silent infarct while the sample is being used to make that analysis.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim 7 is 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 7 uses “and/or” three times, lists “cortical infarcts” twice, and uses grammatically incomplete phrases such as “are silent small noncortical”. It is unclear how these elements of the list are meant to interact.
In one case, the phrase “are silent small noncortical and/or cortical infarcts” would mean “are silent small noncortical infarcts and/or silent small cortical infarcts”. However, this interpretation does not make grammatical sense because the list continues with additional “and/or” uses, “are silent small silent large noncortical” is contradictory and “silent small cortical infarcts” would be listed twice.
In another case, each element is listed as a self-contained element; however, this shares the same grammar problem above in that “are silent small noncortical” is not complete.
A third interpretation is that “and/or” is being used inconsistently. The first and third “and/or” are meant to tie adjectives to nouns (infarcts that are silent small noncortical or silent small cortical; infarcts that are silent large noncortical or silent large cortical) while the second is meant to list alternatives (infarcts that are either small or large, irrespective of if they are cortical or non-cortical). But this creates confusion as to whether the first and second elements are meant to be somehow separate from the third and fourth element.
Clearly, there is some interpretation meant by this combination but it is unclear what each element of the list is meant to recite.
Therefore, claim 7 is indefinite.
Claim 10 is 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.
The term “specialized” is indefinite because it is unclear what the clinic must be specialized for. The clinic may need to be specialized for the care of those with previous silent infarcts, specialized for broader stroke care, or any number of other possibilities for the clinic’s specialty. There is no disclosure in the specification regarding the term “specialized” and one of skill in the art is not clearly apprised of the metes and bounds of how a clinic must be specialized to meet the claim limitations.
Further, the term “specialized” in claim 10 is a relative term which renders the claim indefinite. The term “specialized” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
There is no disclosure which would allow the skilled artisan to understand the metes and bounds of how “specialized” a clinic must be. In the broadest sense, any clinic capable to providing care for infarcts could be “specialized” when compared to a clinic incapable of providing such treatment. In another, there are clinics that may have specific devices, specific therapies, are recognized as top-of-field, or any number of other considerations which may mean a clinic is specialized when compared to one clinic but not another.
The specification only uses the term “specialized” twice (p.33 and p.43) and both only refer to “specialized clinics” without any other information or guidance to evaluate this term.
Therefore, claim 10 is indefinite. For the purpose of this action, a “specialized clinic” will be any clinic that could potentially provide any relevant medical treatment or information. This is according to the broadest, reasonable, ordinary definition of a clinic (Dictionary: “a place in which outpatients are given medical treatment or advice”; form 892).
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-2, 7, 10-12, 16, 20, and 27-28 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 the instantly claimed method in conjunction with a brain imaging methodology, does not reasonably provide enablement for the claimed method absent such imaging. 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.
Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Note that the issues articulated below generally rest on the inadequate guidance to use step b to inform an assessment of whether a subject has had at least one infarct. Claim 17 requires this (the assessment in step c is based on the information gathered in step b) and so is not enabled. The other claims encompass embodiments where steps a-b are unrelated to the assessment in step c; since there are other means of assessing a silent infarct, these claims are rejected for the scope where step b informs the step c assessment.
There are many factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: 1) nature of the invention, 2) breadth of claims, 3) amount of direction or guidance by the inventor, 4) relative skill of those in the art, 5) level of predictability in the art, 6) state of the prior art, 7) existence of working examples, and 8) quantity of the experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The nature of the invention is a method for assessing whether a subject has previously experienced at least one silent infarct. The breadth of the claims is determining an amount of IGFBP7 and comparing this to a generic “reference” and then, independent of that measurement and comparison, assessing whether or not the subject has experienced at least one silent infarct. Claim 17 is the only claim requiring the IGFBP-7 comparison step (b) informs this assessment. By “monitoring the extent” of the silent infarcts, one is necessarily determining whether or not the subject has previously had such an infarct.
The guidance in the specification does not enable the instant assessment. The comparison step does not lead to the ability of the ordinary artisan to assess whether or not the subject has experienced at least one silent infarct as claimed without undue experimentation.
Example 1 (specification p. 45) suggests that circulating IGFBP-7 levels can predict silent brain infarcts. In the data in table 1, IGFBP7 does not differentiate a specific subject as claimed. While the population statistics are significant (p<0.0001), the ranges overlap. For example, a value of 165.8 is the mean of those without silent infarcts but is also within a standard deviation of those with silent infarcts. A person of ordinary skill in the art comparing a value of 163.2 (lower end of a standard deviation for “yes”) to a reference of 165.8 (mean for “no”) would arrive at a conclusion that the subject had not suffered a silent infarct when in fact they had. In the same way, comparing a value of 189.3 (higher end of a standard deviation for “no”) compared to a reference of 186.2 (mean for “yes”) would conclude that the subject had a silent infarct when in fact they had not. While higher levels may indicate a greater possibility that a silent infarct will occur, the prediction of risk is not the same as assessing whether an infarct had actually occurred or not, which is what is claimed; predicting silent infarcts is patentably distinct from the instant assessment and represents non-elected subject matter (Restriction 3/16/26; Response 6/16/26). The method as claimed—comparing IGFBP7 levels to a reference—would not allow the artisan to make the claimed assessment.
The specification also demonstrates certain models which provide different outcomes (table 2). These models also take into account a variety of other factors (age, systolic blood pressure, smoking) which appear required for IGFBP7 to be of use, none of which are currently claimed. Table 2 is also disclosed as assessing the risk of silent brain infarcts (p.47 L9-10), which as above is not the same as the claimed assessment of whether or not the subject had experienced such an infarct in the past. Table 3 is also directed to the prediction of an infarct in combination with other, unclaimed factors (p.47 L19-21), and does not allow the artisan to fairly determine whether the subject has had a previous silent infarct without undue experimentation on the part of others to determine how this information could properly be used to arrive at the claimed conclusion.
Example 2 is the prediction of white matter lesions, which is also non-elected subject matter and does not inform the assessment of a previous silent infarct. Rather, white matter lesions may be caused by a previous silent infarct (specification p. 48 L10) and so may also not be. The presence of a white matter lesion does inherently indicate or even suggest that a previous silent infarct had occurred, only that it is one possibility.
The specification also indicates that the level of IGFBP-7 may not indicate silent lesions, but rather indicates age-related brain diseases (p.48 L19-21). The specification does not disclose which levels of IGFBP-7 or which reference levels would indicate a previous silent infarct vs an age-related brain disease. These diseases are not inherently caused by silent infarcts (e.g., vascular dementia or Alzheimer’s; specification p. 48 L17 L21) and so as with white matter lesions, their presence does not allow the assessment of a previous silent infarct.
While the claim is directed to embodiments including the IGFBP-7 comparison and no more, the open-ended comprising language could include all of the instantly disclosed models and inclusion of additional parameters. However, the art generally does not support this as enabled either.
It is initially noted that the claims are not limited to circulating levels but explicitly include non-circulating levels such as those in tissue (claim 12). There is no reasonable expectation that a circulating protein will have the same correlation to a particular disease state when interrogating a tissue sample.
Further, the specification as discussed above indicates that the IGFBP-7 may also indicate a number of other conditions other than a previous silent infarct, such as predicting future infarcts, white matter lesions, or the presence of an age-related disease. This is further supported by the art. US20150268251 (form 892) teaches circulating IGFBP-7 is increased in subjects with insulin resistance (paragraph 12). US20100285491 (form 892) teaches increased serum IGFBP-7 is indicative of heart failure (paragraph 186). US20140065648 (form 892) teaches levels of IGFBP-7 predict structural or functional heart abnormalities (paragraphs 229, 255, 256). US20150233946 (form 892) teaches levels of IGFBP-7 are indicative of a recent paroxysmal atrial fibrillation (claim 1; paragraph 246). US20150185230 (form 892) teaches IGFBP-7 is indicative of risk of mortality as well as the risk of a cardiovascular event (claim 15).
The guidance in the instant specification as well as that of the art indicates that evaluating IGFBP-7 levels and comparing this to some other value does not allow the artisan to determine any particular outcome much less the past occurrence of a silent infarct. The reference value allowing the prediction of risk is not instantly disclosed as differing from the reference value allowing the assessment of a previous silent infarct. While the method can be practiced—IGFBP7 levels can be determined and compared, followed by an assessment that in no way requires those numbers such as a brain scan—the embodiments where step b somehow informs the assessment in step c is clearly not enabled as it would require undue experimentation on the part of others to determine if and how steps a-b allow for the assessment that a subject has experienced at least one silent infarct.
Therefore, the claims are not fully enabled.
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 1-2, 7, 10-12, 16-17, 20, and 27-28 are rejected under 35 U.S.C. 101 because:
Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A prong 1. Claim 1 and dependent claims thereof 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 recites comparing a naturally occurring level of IGFBP7 to assess whether the subject has experienced one or more silent infarcts. This is the observation of a natural phenomenon and represents a judicial exception. This is explicit in claim 17. Since claim 17 is a further limitation of claim 1, this embodiment is also encompassed by claim 1 and dependent claims thereof.
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 in to 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, the “assessing” step is part of the judicial exception. The other steps (determining, comparing) are the necessary data gathering steps and so are considered insignificant extrasolution activity.
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 “determining” step determines the amount of the biomarker by any means and the Court recognizes this as a routine, conventional activity (MPEP §2106.05(d)(II)). The step of “comparing to a reference” is entirely mental. Further, the combination of measuring a biomarker and comparing the biomarker to a reference was commonplace. See for example:
US 20150185230 claim 15
US 20150233946 claim 1
US 20180231570 (form 892) claim 1
For these reasons, claim 1 is not patent eligible.
Regarding claim 2, the whole of this claim adds to the judicial exception itself, i.e., what the observed phenomenon “indicates”. There are no elements added beyond judicial exception and so is not patent eligible for the same reasons.
Regarding claim 7, the limitations are directed to the type of infarct. Since the assessment of the infarct is part of the judicial exception, the claim is not eligible for the same reasons.
Regarding claim 10, the claim adds two recommendations, intensifying risk factor management, and care is specialized clinics. These are elements in addition to the exception. For the prong 2 analysis, these are generic instructions to “apply it”. Parts a and b are recommendations but do not require that these recommended treatments are actually practiced (mental decisions). The specification is explicit that “recommending” excludes actual treatment (p.15 “applying the actual therapy whatsoever is not comprised by the term”). Increasing risk factor management and providing care in clinics are highly generic and do not provide any particulars regarding how to implement a specific treatment. These essentially cover any possible treatment that a doctor decides to administer and is unrelated to the judicial exception. The claim is generic to the point that it does not even require taking the previous measurements into account. The claim informs a relevant party (such as a doctor) about the implications of the measurement and at best suggests the doctor take this information into account. This is not an integration of the judicial exception but rather the nominal appending of “apply it”. For the 2B analysis, making medical recommendations upon diagnosing a disease is standard in the medical field. See for example NHS (form 892) describing treatment recommendations. The only disclosure in the specification of “risk factor” is atrial fibrillation and so the term is being interpreted as managing atrial fibrillation. Adding anticoagulants is both recommended by NHS as above but also is disclosed by NHS as offered to subjects with atrial fibrillation. The suggestion of adding an anticoagulant is an increase (intensifies) in treatment of atrial fibrillation (management of risk factors). NHS also states that as early as 2007, transfer to community or long-term support is recommended as is being provided access to a “stroke unit”. The instant specification does not provide any definition or examples of a “specialized clinic” and the broadest interpretation of the phrase is any clinic capable of providing care, such as the stroke units or wherever the long-term support is provided. While these recommendations are for stroke, infarcts are a form of stroke; see instant specification at p.4.
Claims 11 and 12 define the subject, which informs others where to observe the natural phenomenon and so is part of the judicial exception itself.
Claim 16 defines the biomarker being observed and so is part of the judicial exception itself.
Claim 17 requires monitoring the extent of the silent infarcts “based on” the comparison step. Similar to the “recommending” step above, there is no particulars of this monitoring and is recited at such a high level of generality that this claim is essentially another instruction to “apply” (based on) the judicial exception.
Claim 20 defines the assay for the determining step. For prong 2, this is still the data gathering step and so is insignificant extrasolution activity. For 2B, this is also a known, routine method of measuring proteins. See:
US 20050118662 (form 892) paragraph 15, 31, 37; claim 9).
US 20090275124 (form 892) paragraph 211, 233, 234.
US 20140065610 (form 892) paragraph 69, 149, 168
Claims 27-28 define the subject, which informs others where to observe the natural phenomenon and so is part of the judicial exception itself.
Therefore, claims 1-2, 7, 10-12, 16-20, and 27-28 are not patent eligible.
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 (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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 7, 11-12, 16, and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Block (US20150233946) in view of Conen (IDS 8/11/23 citation 7).
Regarding claim 1, Block teaches a method of diagnosing ongoing atrial fibrillation (AF) in a subject comprising a) determining the amount of IGFBP7 in a sample from the subject and comparing that amount to a reference amount (claim 15). This meets the limitations of instant claim 1 steps a and b.
Block does not teach instant step c of “assessing whether the subject has experienced one or more silent infarcts”.
Conen teaches patients with atrial fibrillation are at increased risk of cognitive decline (abstract). Conen further teaches that patients with AF have a high burden of brain lesions where “most of these lesions are clinically silent” (abstract). Patients with known AF were submitted to brain MRI to quantify previous silent lesions, i.e., assess whether the patients had experienced one or more silent infarcts. This meets the limitations of instant step c.
At the time of filing, it would have been obvious to a person of ordinary skill in the art to combine these teachings, arriving at the instant claim. Instant steps a and b are taught by Block as diagnosing ongoing atrial fibrillation. Conen is also concerned with atrial fibrillation and teaches that those subjects suffering AF (such as those subjects in Block) are at higher risk of cognitive decline and are likely to have experienced one or more silent infarcts. Further, these infarcts are taught as indicative of worse cognitive function (Conen, abstract), Conen stating that “clinically silent infarcts on brain MRI approximately doubled the risk of dementia and led to a steeper decline in cognitive function” (p.996 C1). Thus, once a subject is identified as having ongoing AF according to Block by determining and comparing the amount of IGFBP7 in a subject sample, it would have been obvious to assess whether the subject has experienced at least one silent infarct by MRI according to Conen because these silent infarcts provide useful data regarding ongoing risk and prognosis. This meets every limitation as instantly claimed and so claim 1 would have been obvious.
Regarding claim 2, this claim recites what the comparison step is “indicative” of. This is an inherent property of the gathered data. An amount of IGFBP7 larger than a reference is indicative of a subject suffering from at least one silent infarct whether or not this fact was known at the time. Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Further, MPEP § 2112 (II), "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).”
Regarding claim 7, Conen teaches the silent infarcts include large non-cortical or cortical infarcts as well as small noncortical infarcts (abstract).
Regarding claim 11, the subject suffering atrial fibrillation is addressed above.
Regarding claim 12, both Block (claim 17) and Conen (p.991) teach the subjects (patients) are human. Further, Block teaches the sample is, e.g., blood (claim 5).
Regarding claim 16, Block teaches the IGFBP-7 is a polypeptide (paragraphs 82, 84).
Regarding claim 27, Block teaches the subject may be older than 65 years (paragraph 46), making such a subject an obvious choice. Conen also teaches including patients 65 years or older (p.991 C1).
Regarding claim 28, Conen teaches the silent infarcts occur in patients with no history of stroke or TIA (p.992 C1-C2; table 1,2) while Block also teaches the subject preferably has no history of stroke (paragraph 59). These teachings would have made it obvious to include these subjects in the above method because both documents teach their relevant portions of the method in the context of subjects with no such history.
Therefore, claims 1-2, 7, 11-12, 16, and 27-28 would have been obvious.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Block (US20150233946) in view of Conen (IDS 8/11/23 citation 7) as applied to claims 1-2, 7, 11-12, 16, and 27-28 above, and further in view of Brandes (form 892).
The teachings of Block and Conen are discussed above and incorporated herein.
Regarding claim 10, Conen teaches anticoagulation treatment is not associated with higher microbleed counts (p.994 C2). Conen teaches anticoagulation effectively prevents stroke in patients with AF but that anticoagulation may not be sufficient to prevent a significant number of silent infarcts (p.998 C1). As above, Conen also teaches silent infarcts are associated with a higher risk of cognitive decline. Conen teaches adding rivaroxaban to aspirin therapy is better than aspirin alone (p.998 C1); including additional therapeutics meets the limitation of “intensifying”.
One of ordinary skill in the art would have found it obvious to recommend anticoagulation therapy to those subjects not currently engaged in such therapy, intensifying existing therapy, improving risk factor management, and providing care in specialized clinics. See MPEP 2141(II)(C): "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. In this case, Conen teaches most of the subjects were on anticoagulant therapy and that this therapy is effective to prevent stroke in patients with AF, which is a desirable outcome. As such, it would have been obvious that if a subject with AF is not currently on any form of anticoagulation therapy, that subject should begin such therapy. Going from no anticoagulation therapy to any amount of such therapy also meets the limitations of intensification of anticoagulation therapy. Thus, based on the teachings in Conen of the benefits of anticoagulation therapy and that this therapy was not associated with microbleeds, it would have been obvious to recommend starting (intensifying) anticoagulation therapy.
Additionally, Brandes is also concerned with patients with AF and teaches that early management of underlying conditions improves outcomes in subjects with AF (abstract). Brandes teaches the benefits of expanding risk factor management to improve outcomes and reduce AF burden (p.119 C1-C2). It would have been obvious to intensify risk factor management in those with atrial fibrillation (such as those in Block) because Brandes teaches the importance of increased, broad risk factor management in these same subjects. Brandes also suggests “a dedicated multidisciplinary AF team or clinic systematically coordinating the patient care” (p. 124 C2), which would have made obvious care in such a clinic to gain these benefits. A clinic containing a “multidisciplinary team” specifically for the treatment and management of AF appears to meet the broadest reasonable definition of “specialized clinic”.
Therefore, claims 1-2, 7, 10-12, 16, and 27-28 would have been obvious.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Block (US20150233946) in view of Conen (IDS 8/11/23 citation 7) as applied to claims 1-2, 7, 11-12, 16, and 27-28 above, and further in view of Spinke (US20050118662)
The teachings of Block and Conen are discussed above and incorporated herein. As above, Block teaches determining the amount of IGFBP-7 polypeptide. Block teaches determining IGFBP-7 by sandwich ELISA where the capture antibody (first monoclonal antibody) is conjugated to biotin (biotinylated) (paragraph 245). Block does not use a ruthenylated Fab’2 antibody for the detection (second) antibody. However, Block does a ruthenylated detection (second) antibody when detecting IL-6 (paragraph 239).
Spinke also teaches methods of detecting biomarker proteins including NT-proBNP (claim 1), which is also a protein also measured in Block (paragraph 9, 13, claim 1). Spinke teaches various ways of measuring biomarkers including a biotinylated capture antibody and a ruthenylated F(ab’)2 detection antibody in a sandwich ELISA (paragraph 35).
It would have been obvious to use a known method of detecting proteins to detect IGFBP7. ELISA was a well-established immunoassay for detecting proteins and one of ordinary skill in the art could have adapted the MAB specific ELISA of Spinke to utilize IGFBP7 specific antibodies with predictable results. Attaching a ruthenium label to an antibody was known and achieves predictable results; this label is taught in Spinke above and Block characterizes it as a “typical label” (paragraph 90). The F(ab’)2 format was further well-known and predictable. Block teaches the antibodies disclosed include F(ab)2 fragments (paragraph 89) and Spinke teaches this format (paragraph 35).
Therefore, claims 1-2, 7, 11-12, 16, 20, and 27-28 would have been obvious.
Conclusion
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/Adam Weidner/ Primary Examiner, Art Unit 1675
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