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 .
Remarks
In response to communications sent January 5, 2023, claim(s) 1-10 are pending in this application; of these claim 1 is in independent form.
Response to Amendment
The preliminary amendments to the claims and specification that were filed January 5, 2023 are acknowledged and have been entered into the record.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The priority date of each claim cannot be determined because the priority document is in a foreign language. Therefore, the Examiner will note pertinent intervening art.
Drawings
The drawing(s) filed on January 5, 2023 are accepted by the Examiner.
Information Disclosure Statement
The Information Disclosure Statement(s) is/are acknowledged and the references contained therein have been considered by the Examiner. This includes the Information Disclosure Statements(s) filed on: January 5, 2023.
Claim Objections
Claims 2-10 are objected to because of the following informalities: the dependent claims use the indefinite article (e.g., “a method of claim 1”) instead of the definite article (e.g., “the method of claim 1”). Appropriate correction is required.
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 5-7 and 10 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.
Regarding claim 5, the phrase “before performing the Raman spectroscopy” is ambiguous, because it implies that “performing the Raman spectroscopy” is indeed a step of the claimed method in claim 1 (and dependent claims). However, the first element of claim 1 may be interpreted as “providing, as input data,…”. That is, the performance of the Raman spectroscopy in claim 1 may be a “product-by-process” element that limits the structure of the “input data”. Under that interpretation, “performing the Raman spectroscopy” is not a positively recited step. Therefore, claim 5 is ambiguous because it occurs “before” a step that is not necessarily part of the method.
Regarding claims 5 and 10, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). While an “optional” limitation is sometimes permitted in a claim, it is unclear whether the “preferable” nature of the element was intended to be a required limitation rather than an optional limitation.
Regarding claims 6-7, the phrase "can be defined" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 5 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 5 limits a step of “performing the Raman spectroscopy”, but this step is not a positively recited step in claim 1. Performing Raman spectroscopy would involve light scattering, whereas the steps in claim 1 provide “input data”. 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.
Suggestion for compact prosecution: The Examiner suggests amending the claims rather than cancelling the claims because steps that are not abstract affect analysis under 35 U.S.C. § 101. Therefore, is no current rejection of claim 5 under 35 U.S.C. . § 101.
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 1-4 and 6-9 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) mathematical calculations. This judicial exception is not integrated into a practical application because the input data cover all uses of the judicial exception. This is partly because the element of “input data” is an element limited as a product-by-process limitation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because providing input data is well-understood routine and conventional; see buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) regarding “computer receives and sends information over a network” as noted in MPEP §2106.05(d) II.
Note that claim 5 is not rejected under 35 U.S.C. § 101 because “performing the Raman spectroscopy, the fecal sample protein extract is homogenized, preferably by centrifugation” is not routine and conventional for detecting inflammatory bowel disease using Raman data from the fecal sample.
Note that claim 10 is not rejected under 35 U.S.C. § 101 because “a Raman spectrometer connected to a detector… is used to obtain the Raman spectrum of the fecal sample protein extract” (portions omitted) is not routine and conventional for detecting inflammatory bowel diseases.
1. A diagnosis method for detecting inflammatory bowel diseases comprising Ulcerative Colitis (UC) and Crohn's Disease (CD) (the intended use in the preamble does not limit the claim as a positively recited step in the body of the claim), the method comprising the following steps
a) providing, as input data, a Raman spectrum of a protein extract of a fecal sample (an additional element beyond the abstract ideas; however, providing the input data is not a positively recited step of performing a Raman spectrum of a protein extract of a fecal sample; instead, only data is provided in this step; therefore, the actual Raman spectrum is input data that is limited as a product-by-process claim; because the inputted data is defined by product-by-process, the data that can be inputted is broad enough to encompass any use of the judicial exception; therefore, it is insignificant pre-solution activity; and providing input data is well-understood routine and conventional; see buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) regarding “computer receives and sends information over a network” as noted in MPEP §2106.05(d) II );
b) isolating, from said Raman spectrum, a band in a wavenumber range of about 1550-1750 cm.sup.−1, which defines amide-I vibration modes (mathematical calculation);
c) calculating a second derivative profile of said band of Raman spectrum, and identifying the minima of said profile (mathematical calculation);
d) performing a deconvolution of said band, setting a number of sub-bands equal to the number of the minima of said second derivative profile, obtaining a number of sub-bands equal to at least said number of minima, each sub-band having a respective center-frequency ω.sub.i and a respective area A.sub.i, with i=1, 2, . . . n (mathematical calculation);
e) associating the sub-bands obtained in step d), based on the center-frequency ω.sub.i thereof, with corresponding vibration modes of protein secondary structures comprising vibration modes of disordered protein secondary structures of amide-I and vibration modes of the higher frequency anti-parallel β-sheet protein secondary structures (mathematical calculation);
f) calculating a ratio R of the area of the sub-band, associated with the vibration modes of the disordered protein secondary structures of amide-I, with the area of the sub-band associated with the vibration modes of the higher frequency anti-parallel β-sheet protein secondary structures (mathematical calculation);
g) verifying that the ratio R is greater than or equal to a first threshold value to confirm that the protein extract of the fecal sample belongs to a patient suffering from an inflammatory bowel disease (mathematical calculation with a particular intended purpose of confirmation).
2. A method according to claim 1, wherein after step g) if said ratio R is greater than or equal to a second threshold value, the protein extract of the fecal sample belongs to a patient suffering from Ulcerative Colitis (UC), while if said ratio R is lower than said second threshold value, the protein extract of the fecal sample belongs to a patient suffering from Crohn's disease (CD) (limitations to the mathematical calculations that are still mathematical calculations).
3. A method according to claim 1, wherein in step d) in order to perform the deconvolution, a minimum number of parameters characterizing each sub-band is left free, and an iterative best-fit procedure is started, which thus uses said minimum number of parameters for each sub-band, preferably using a Voigt profile for each sub-band, each Voigt profile being mathematically expressed by a convolution of a Lorentzian curve with a Gaussian curve, and the characteristic parameters of which defining said minimum number of parameters comprise: the center-frequency ω.sub.Vgt; the amplitude a.sub.Vgt; the half-width Γ.sub.VG related to the half-width at half-height of the Gaussian Γ.sub.G, being Γ.sub.G=Γ.sub.VG√{square root over (2 ln 2)}, and the half-width Γ.sub.VL depending on the ratio of the half-width at half-height of the Lorentzian Γ.sub.L with respect to said half-width Γ.sub.VG, being Γ.sub.L=Γ.sub.VG.Math.Γ.sub.VL (mathematical calculations).
4. A method according to claim 1, wherein between step a) and step b) a fit of a region of the Raman spectrum between 1300-1800 cm.sup.−1 is performed setting a predetermined profile, preferably a Voigt profile; preferably wherein, to obtain said fit, a deconvolution is performed, leaving a minimum number of parameters characterizing each sub-band free, and an iterative best-fit procedure is started, which thus uses said minimum number of parameters for each sub-band, preferably using a Voigt profile for each sub-band, each Voigt profile being mathematically expressed by a convolution of a Lorentzian curve with a Gaussian curve, and the characteristic parameters of which defining said minimum number of parameters comprise: the center-frequency ω.sub.Vgt; the amplitude a.sub.Vgt; the half-width Γ.sub.VG related to the half-width at half height of the Gaussian Γ.sub.G, being Γ.sub.G=Γ.sub.VG√{square root over (2 ln 2)}, and the half-width Γ.sub.VL depending on the ratio of the half-width at half-height of the Lorentzian Γ.sub.L with respect to said half-width Γ.sub.VG, being Γ.sub.L=Γ.sub.VG.Math.Γ.sub.VL (mathematical calculations).
6. A method according to claim 2, wherein said first threshold value can be defined by performing the following steps:
providing, as input data, a Raman spectrum of a fecal sample protein extract for each patient of a first known group of patients with Ulcerative Colitis (UC) or Crohn's Disease (CD) and for each patient of a second known group of healthy patients (an additional element beyond the abstract idea of providing data);
for each patient, of both the first group and second group, isolating from the respective Raman spectrum the band in the wavenumber range of about 1550-1750 cm.sup.−1 (mathematical calculations);
performing steps c), d), e) and f) for each Raman spectrum (mathematical calculations);
performing an analysis of a first ROC curve considering the ratios R of the first group and the second group as database and calculating the first threshold value by Youden's index (mathematical calculations).
7. A method according to claim 6, wherein said second threshold value can be defined by performing the following steps:
providing, as input data, a Raman spectrum of a fecal sample protein extract for each patient of a first known subgroup of said first group consisting of patients with Ulcerative Colitis (UC) and for each patient of a second known subgroup of said first group consisting of patients with Crohn's Disease (CD) (an additional element beyond the abstract idea of providing data);
for each patient, of both the first subgroup and the second subgroup, isolating from the respective Raman spectrum the band in the wavenumber range of about 1550-1750 cm.sup.−1 (an additional element beyond the abstract idea of providing data);
performing steps c), d), e) and f) for each Raman spectrum (an additional element beyond the abstract idea of providing data);
performing an analysis of a second ROC curve considering the ratios R of the first subgroup and the second subgroup as database and calculating the second threshold value by Youden's index (an additional element beyond the abstract idea of providing data).
8. A method according to claim 2, wherein said second threshold value is greater than said first threshold value (limitations to the mathematical calculations that are still calculations).
9. A method according to claim 1, wherein the Raman spectrum is acquired in a wavenumber range between 400 cm.sup.−1 and 3300 cm.sup.−1, preferably between 500 cm.sup.−1 and 2000 cm.sup.−1 (this element is not a positively recited step; instead, it is a product-by-process type element that describes the structure of the Raman spectrum data; therefore, the portion of the claim that it limits is still an abstract idea).
Allowable Subject Matter
Claims 5 and 10 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The closest art is Pence, I. J., et al. "Endoscopy-coupled Raman spectroscopy for in vivo discrimination of inflammatory bowel disease." Biomedical Vibrational Spectroscopy VI: Advances in Research and Industry. Vol. 8939. SPIE, 2014.
However, the Pence reference does not teach the particular “protein extract” as claimed. Additional art cited on the I.D.S. and PTO-892 do not teach the combination of the protein extract of fecal matter with the particular analytical steps.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pence, I. J., et al. "Endoscopy-coupled Raman spectroscopy for in vivo discrimination of inflammatory bowel disease." Biomedical Vibrational Spectroscopy VI: Advances in Research and Industry. Vol. 8939. SPIE, 2014.
Does not involve a “protein extract” as claimed.
US-20220390375-A1 pertinence: general purpose handheld Raman-based diagnostic
WO-2020240399-A1 pertinence: different inventive entity, but related inventive entity; involves Amide I and Raman deconvolution. Also, US-20220299526-A1.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jesse P Frumkin whose telephone number is (571)270-1849. The examiner can normally be reached Monday - Friday, 10-5 ET.
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/JESSE P FRUMKIN/ Primary Examiner, Art Unit 1685 June 15, 2026
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