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 .
Response to Amendment
Claims 1-320 and 330-340 have been cancelled in the amendment filed on 3 July 2025. Following the amendment, claims 321-329 are pending in the instant application, and are under examination in the instant office action.
Election/Restrictions
Applicant’s election of Group I (claims 321-329) in the reply filed on 3 July 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/US2020/045687 filed on 11 August 2020, which claims the benefit of US Provisional Application Nos. 62/885,413 filed on 12 August 2019; 62/035390 filed on 14 November 2019; and 63/035,390 filed on 5 June 2020.
Claims 321-329 have an earliest effective US filing date of 12 August 2019.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 10 February 2022 and 3 July 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner.
Claim Objections
Claim 321 is objected to because of the following informalities: the claim contains the abbreviations Ab-1 and Ab-3 which are not spelled out upon their first appearance within the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 321-329 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 321 uses the terms “Ab-1” and “Ab-3” as limitations but when read in light of the specification these terms appear to be inconsistent with the terms used in the art for these elements (see Table 2, pg. 44 of the Specification). Since it is improper to import limitations into the claim from the specification, without a reference to a known antibody, one cannot determine the metes and bounds of “Ab-1” and “Ab-3”. Moreover, because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of “Ab-1” and “Ab-3”, an artisan cannot determine if an antibody meets the limitations of the claim. This affects the scope of all depending claims.
Claim 321 is further indefinite wherein it recites functional language (“a substance capable of engaging with the detection agent and creating a detectable and quantifiable signal”) without any positively recited active method steps whereby that signal is detected and quantified. Without active steps, it is unclear if detection and quantification are required for infringement of this claim; or if only incubating is required. Thus, the substance is limited by what it does rather than what it is materially and the scope of the claims is indefinite. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since the claims fail to meet all (3) criteria set forth in MPEP 2173.05(g), then Claim 321 is rejected. Again, this rejection affects the scope of all depending claims.
Claim 321 is further indefinite wherein it states: “determining the concentration of frataxin protein with a limit of detection of less than 0.5 pg/mL”. Normally detection limits are stated as a range. Since this claim requires detection of less than 0.5 pg/mL, and there is only one detection/determining step, then this is read as the concentration of frataxin is equivalent to “less than 0.5 pg/mL”.
Claim 322 is indefinite when read in light of the specification. This claim fails to further limit the scope of the parent claim; rather, it adds a step that precedes the first step of the parent claim. Increasingly the order of methods steps has been clarified in interference. The courts have held that the listing order is important and will be given limiting effect. Thus in process/method claims, whenever possible claim steps should be written in the order in which they should be performed (See Mformation Tech v. Research-in-Motion, Fed. Cir. 2014 and Phillips v. AWH, Fed. Cir. 2005). The elements of a method claim are usually recited in temporal sequence, if one step modifies another, the modifying step should precede the modified step (Altiris, Inc. v. Symantec Corp. (2003)). Claim 322 modifies the method of Claim 321 and does not further limit the steps of the parent claim, but rather temporally precede those of the parent. For these reasons, the claim is indefinite when read in light of the specification.
Claim 324 is indefinite when read in light of the specification. The claim recites “the substrate comprises assay beads and helper beads”. Again, this is an attempt to limit a claimed element by what it does functionally (acts as a “helper”), rather than what it is structurally/materially. The specification provides no definition for “helper beads”. This claim depends from claim 321, which merely states “a substrate comprising a capture agent”. Thus, when read in the context of the parent “capture agent” it is unclear what falls within the scope of a “helper bead” versus an assay bead. Therefore, a person having ordinary skill would not know what beads fall within the metes and bounds of the claim, or when this limitation was directly infringed.
Claims 325-329 are indefinite wherein they recite concentrations of frataxin that are outside the scope defined in the parent claim. Claim 321 states: “determining the concentration of frataxin protein with a limit of detection of less than 0.5 pg/mL” (see above for interpretation of this limitation) and this is taken to mean the concentration detected is less than 0.5 pg/mL. However, claims 325-329 recite concentrations that are different than the less than 0.5 pg/mL required by the parent claim. Claims 325-327 state, “the serum sample is below 10 pg/mL” and “the concentration of frataxin protein present in the CSF sample is below 5 pg/mL”. Claims 328-329 state, “the concentration of frataxin protein present in the biofluid sample is at least 2- fold to at least 2000-fold less than the concentration of frataxin protein present in a biofluid sample from an age-matched healthy subject”, which may broaden the scope of the concentrations beyond the less than 0.5 pg/mL recited by the parent claim.
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 321-329 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea judicial exception and a natural correlation judicial exception without significantly more. The claim(s) recite(s) “determining” (claim 321) and diagnosing (claims 325-329) a subject as having Friedreich’s Ataxia if levels of frataxin, in either serum or CSF, are below a specified amount. These judicial exceptions are not integrated into a practical application because there are no additional elements that provide any of the considerations for integration listed in MPEP 2106.05(a-c), (e) and (h). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s) itself because this claim does nothing more than append the judicial exceptions abstract ideas of determining and/or diagnosis to the observation of the natural phenomenon judicial exception itself.
The claims are directed to a method for determining the concentration of frataxin and diagnosing Friedreich’s Ataxia in a human subject comprising detecting serum levels of frataxin protein below a specified level. Methods are one of the statutory categories of invention (STEP 1:YES).
The claims recite “determining” and “diagnosing”, both of which are abstract mental concepts that belong to enumerated group (c) of the Abstract Idea Groupings described in MPEP § 2106.04(a)(2): Mental processes — concepts performed in the human mind (including an observation, evaluation, judgment, opinion). But more importantly, the claims recite a natural correlation/phenomenon/law of nature (hereafter “natural phenomenon” but these terms are used interchangeably) whereby -Friedreich’s Ataxia pathology is correlated with decreases in the concentration of frataxin protein in serum and CSF. Therefore, the claims recite at least one judicial exception (STEP 2A, Prong One: YES). Analysis may proceed for only one of these judicial exceptions.
According to Step 2A, Prong Two, set forth in set forth in MPEP 2106.04 II A (2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. These considerations are set forth in MPEP 2106.05 (a) through (c), (e), and (h). This analysis turns to the additional steps/elements recited within the claim. Independent claim 321 requires: implicitly obtaining a biofluid sample, incubating said sample with a capture agent comprising Ab-1 and a detection agent comprising Ab-3; then incubating the substrate with a substance capable of engaging with the detection agent thereby determining the concentration of frataxin protein with a limit of detection of less than 0.5 pg/mL. There are no additional elements within claim 325 aside from diagnosing. It is unclear if Ab-1 and Ab-3 of the claims are novel within the art. It is assumed that Ab-1 and Ab-3 are antibodies, and therefore the claims read on an immunoassay, but determining is recited at a high level of generality such that it covers every viable means for determining known in the art (see MPEP 2106.05(e)). Depending claims add adjunct methods such as neuroimaging, recited at a high level of generality, and determining the concentration of neurofilament, which is not limited to an immunoassay and is recited at a high level of generality so as to cover all means of detecting known in the art before the filing date of the application.
There are no additional elements that reflect any improvement within the technical field; there are no additional elements that apply the abstract idea or natural phenomena judicial exceptions to any particular treatment/prophylaxis or which utilize any particular machine. There are no additional elements that effect a transformation; nor are there additional elements that apply the judicial exception in some other meaningful way beyond generally linking it to a field, namely, Friedreich’s Ataxia (FRDA). Therefore, there are no additional steps/elements that integrate the judicial exception(s) of the claims into a practical application ((STEP 2A, Prong Two: NO).
Regarding the method claimed, the specification itself states that the elements/steps of the claims were known in the art prior to filing: Variants of frataxin were known in the art (paragraph [0111]); The preparation of antibodies, whether monoclonal or polyclonal, may be carried out using any methods known in the art (paragraph [0165]); and, the assay methods and systems may employ a variety of different components, steps, and/or other aspects that will be known and understood by those of ordinary skill in the art (paragraph [0186]). Additionally, all of the antibodies disclosed in the specification were commercially available prior to filing (Table 2, pg. 44). Therefore, in in accordance with MPEP 2106.07(a)(III)(A), the examiner has cited express statements in the specification indicating that the additional elements were sufficiently well-known 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 MPEP 2106.07(a)(III)(C), 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 carriers and FRDA patients show significantly lower amounts of frataxin protein compared to controls (50.5% of control, p <<< 0.0001, and 21.1% of control, p <<< 0.0001, respectively, Figs. 2A and B of Deutsch et al. Mol Genetics and Metabol., 101: 238-245, 2010). The authors teach a rapid, lateral flow immunoassay can be used to noninvasively assess disease severity in FRDA patients, measure frataxin levels in a clinical research study format, and serve as a complementary diagnostic tool. This assay identifies differences in frataxin protein levels between controls, carriers, and patients in buccal cells and whole blood. Protein extracted from purified PBMCs and platelets also showed clear differences (data not shown)” (pg. 243, Discussion, first paragraph). Other studies demonstrate that levels of plasma neurofilament (instant claims 326-329) were known to be significantly higher in FRDA patients than controls (Abstract Results, Zeitlberger et al., Frontiers in Cellular Neurosci., 12:366, 2018). Still other prior art references demonstrate that structural brain damage as seen on neuroimaging was known to occur in FRDA, as required by instant claim 326 (Abstract, Valva et al., Frontiers in Neurology, 9, article 747, 2018). Specifically, the authors report, grey matter volume reduction in FRDA compared to controls, as well as, a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial white matter (Abstract), which specifically teaches the requirements of the claim (“gray matter volume loss”; “increased mean diffusivity in white matter; increased axial diffusivity in white matter; and increased radial diffusivity in white matter”). Therefore, the steps/elements recited in addition to the judicial exception were all well-understood, routine, conventional activities in the field of FRDA 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 FRDA diagnosis.
For all of these reasons, Claims 321-329 are directed to the judicial exception without significantly more and are rejected.
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 321-323, 325 and 328 are rejected under 35 U.S.C. 103 as being unpatentable over Lazaropoulos et al., Annals of Clinical and Translational Neurology, 2(8): 831-842, 2015, as evidenced by the abcam publication list for the Anti-frataxin antibody [18A5DB1] citing Lazaropoulos and the Pierce ECL websheet; and in further view of Guo et al., Analytical Chemistry, 90: 2216-2223, 2018.
Regarding claim 321, the Lazaropoulos prior art reference teaches a method for determining the concentration of frataxin protein in a biofluid sample, namely, whole blood samples (pg. 832, Methods, Frataxin assay). The authors use a Western blot assay in which proteins from the sample were separated by SDS-PAGE (pg. 832, last paragraph). These proteins were then transferred to nitrocellulose and incubated the substrate with the detection agent comprising Ab-3 of the instant claims (Abcam mouse anti-frataxin antibody; see Table 2 of the instant specification). While Lazaropoulos does not identify this antibody as the same anti-frataxin antibody [18A5DB1] as Table 2 of the instant specification, the abcam publication list for this antibody cites Lazaropoulos as using this antibody therefore it is provided solely as evidence that this is the same antibody as claimed. The Lazaropoulos et al. prior art method then incubates the blot with a “substance capable of engaging with the detection agent and creating a detectable and quantifiable signal”, namely, horseradish peroxidase (HRP)-conjugated secondary antibodies. Figure 2C demonstrates FRDA patients have about 50% of less levels relative to control blood levels.
Regarding claim 322, additionally the Lazaropoulos prior art teaches immunoprecipitation assays comprising whole blood or blood fractions (see pg. 833, paragraph bridging columns, and Figure 6B). In these methods protein G beads are incubated with the mouse anti-frataxin antibody that is the same “Ab-3” of the instant claims. This teaches incubating the substrate with the capture agent before incubating with the biofluid sample and detection agent. The beads are reacted with blood samples and then detected by extracting bound proteins and running them through the same SDS-PAGE and nitrocellulose methods as Western blot.
Regarding claim 323, the Lazaropoulos prior art teaches incubating of capture agent with sample for 2 hours (pg. 833, column 2, lines 2-3), which teaches the 120 minutes of the instant claim part (iii). The prior art utilizes Pierce enhanced chemiluminescence (ECL) kit for detection (pg. 832, last line) but does not disclose how long the detection agent is incubated. The Pierce ECL product websheet is provided as evidence that the working solution only has a stability of 1 hour. Therefore, the 1 hour workability of prior art reagents, renders obvious the “about 30 minutes” of instant claim part (iii) for the detection method of part (b). Further, the Court has stated that, generally, such differences of incubation duration amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421. MPEP 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular incubation time of about 30 minutes is critical, because paragraph [0032] discloses the incubation step of (b) occurs for about 10-150 minutes.
The only element that the Lazaropoulos reference is silent on is the Ab-1 antibody of instant claim 321, which the specification states is LSBio catalog # LS-C760752.
The Guo et al. prior art reference, however, remedies this deficiency by teaching methods comprising an antifrataxin antibody (clone 1D9) from LifeSpan Biosciences, which is identical to the antibody of Ab-1 of the claims. Guo et al. use this antibody in assays comprising blood biofluid samples and teach erythrocytes from FRDA patients have frataxin levels equal to 17 ng/mL blood; platelets have 1.0 pg/μg protein frataxin and PBMC have 2.7 pg/μg protein frataxin, all of which are significantly lower than the levels in control patients (Table1). Therefore, the Guo et al. prior art renders obvious the method of instant claim 325 wherein a frataxin protein is present in blood biofluid sample below 10 pg/mL. Additionally, the Guo et al. prior art teaches FRDA patients have >2-fold less frataxin in their blood erythrocytes, platelets and PBMCs (Table 1). This teaches “frataxin protein present in the biofluid sample is at least 2-fold to at least 2000-fold less than the concentration of frataxin protein present in a biofluid sample from a healthy subject” as required by instant claim 328.
It would have been obvious to a person having ordinary skill in the art, before the effective filing date of the application to use the Ab-1 antibody of the instant claims equivalent to the antifrataxin antibody (clone 1D9) from LifeSpan Biosciences as the capture agent in the methods disclosed by Lazaropoulos. Given that Guo et al. demonstrate a similar efficacy in detecting frataxin in human blood samples, a skilled artisan would have been able to make this substitution with predictable success in “determining the concentration of frataxin protein in a biofluid sample” as claimed.
Therefore, the method of the invention is prima facie obvious in view of the elements and known methods disclosed in the art before the filing date of the application, and claims 321-323 are rejected.
Claims 326-327 are rejected under 35 U.S.C. 103 as being unpatentable over Lazaropoulos et al., 2015, as evidenced by the abcam publication and the Pierce ECL websheet; taken with Guo et al., 2018 as applied to claims 321-323, 325 and 328 above, and further in view of Zeitlberger et al., 2018 and Valva et al., 2018 (cited in full above).
The teachings of Lazaropoulos et al., the abcam publication, the Pierce ECL websheet; and Guo et al., 2018 as they pertain to the inventions of claims 321-323 and 325, are outlined in the rejection above.
Regarding claim 326, none of the references teach the method further comprising determining the concentration of neurofilament light (NFL), wherein if the concentration of NFL is at least 20 pg/ml in serum or 1200 pg/mL in CSF (instant claim 326). The Zeitlberger et al. prior art, however, remedies this deficiency by disclosing mean plasma (a.k.a. “serum” of the claim) NFL is higher in FRDA patients relative to levels in controls. Specifically, the prior art teaches: “Plasma NfL and GFAP concentrations were significantly higher in FRDA patients than in controls (17.10 vs. 7.61 pg/mL, p < 0.001 and 99.00 vs. 59.50 pg/mL, p = 0.006, respectively)” (pg. 4, Results, third paragraph), which teaches serum NFL levels of at least 20 pg/ml in FRDA patients. While the Zeitlberger art does not specifically disclose the claimed limitation “diagnosing the subject”, but as stated above (Rejection under 101), this is a mental process judicial exception that cannot be the subject matter that distinguishes the instant claims over the prior art because it is non-statutory subject matter.
It would have been obvious to a person having ordinary skill in the art, before the effective filing date of the application, to combine the teachings of Lazaropoulos et al., the abcam publication, the Pierce ECL websheet; and Guo et al., 2018 with the teachings of Zeitlberger. Motivation to combine these teachings wherein it discloses the frataxin protein is heavily degraded by the ubiquitin-proteasome pathway, which as the name implies, is ubiquitous within the human body. Therefore, frataxin protein levels may not accurately reflect disease (pg. 7, first paragraph), and other brain-derived proteins, such as NFL, are required (pg. 4, Discussion first paragraph).
Regarding claim 327, while the combined teachings of Lazaropoulos et al., Guo et al., 2018; and Zeitlberger et al. disclose the blood concentration of frataxin protein is below 10 pg/mL and the concentration of neurofilament light chain present in the serum sample is at least 20 pg/mL in FRDA patients, these references fail to disclose the method “the further comprising performing a neuroimaging assessment on the subject, wherein the subject is diagnosed with Friedreich's Ataxia if: a) the neuroimaging assessment shows one or more of: gray matter volume loss; lobular atrophy; spinal cord atrophy; mean volume loss of dentate nucleus; reduced fractional anisotropy in white matter; increased mean diffusivity in white matter; increased axial diffusivity in white matter; increased radial diffusivity in white matter; increased mean diffusivity in cervical spinal cord; increased axial diffusivity in cervical spinal cord; increased radial diffusivity in cervical spinal cord; increased mean diffusivity in cerebellar peduncles; increased axial diffusivity in cerebellar peduncles; increased radial diffusivity in cerebellar peduncles; accumulation of iron in dentate nuclei; and increased admixture of iron, copper, and zinc in dentate nuclei in the subject, as compared to an age-matched healthy subject”. The Valva et al., 2018 reference, however, remedies this deficiency by teaching grey matter volume reduction in FRDA compared to controls, as well as, a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial white matter (Abstract). This, teaches the requirements of instant claim 327 (“gray matter volume loss”; “increased mean diffusivity in white matter; increased axial diffusivity in white matter; and increased radial diffusivity in white matter”).
Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalence for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). This case law applies to the instant claims because Lazaropoulos teach blood frataxin protein is below 10 pg/mL in FRDA patients; Zeitlberger disclose the concentration of neurofilament light chain present in the serum sample is at least 20 pg/mL in FRDA patients; and Valva disclose specific neuroimaging features distinguish FRDA. Thus, it is prima facie obvious to combine these elements, each of which are taught by the prior art to be hallmarks of Friedreich’s ataxia.
Therefore, the invention of the instant claims is obvious in view of what was disclosed in the art prior to the filing date of the application.
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