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 .
Detailed Action
Summary
This is the Non-Final Office Action based on application 18/021229 RCE filed 08/31/2026.
Claims 1, 5 & 6 are pending and have been fully considered.
Claims 2-4 are cancelled.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/31/2026 has been entered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 & 5-6 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.
With respect to Claim 1, there is a clarity issue which is the preamble is drawn towards “diagnosing,” which is a mental process, but what is clearly being done in the claim body is detecting/detection. Therefore, the claimed diagnosing is confusing.
The proposed edits below should solve this issue. Notably the proposed edits are for the preamble which is drawn towards, “a detection method for diagnosing acting of nervonic acid,” and the last line in the claim reads, and “administered a dose of 0.03g/kg/d of nervonic acid.”
These sections of the claim should read “a method for detecting acting of nervonic acid,” and “administered a dose of 0.03g/kg/d of nervonic acid in the products containing nervonic acid.”
With respect to Claim 5, it is unclear it is unclear if applicant means the “solvent,” and “solutes,” to indicate that the compounds are mixed together or if they are separated out in the claimed kit. Since the kit requires “liquid A,” and “liquid B,” and then seemingly separation of solutes from solutes, this is unclear if the claimed kit requires only separation of liquid A from liquid B or if there is more than that.
Further with respect to Claim 5, the term “standard,” is relative and not defined by the claim. What one person considers, “standard,” another might not, so this is unclear for the claimed kit if the “standard,” substances are any different than just normally found SM(d17: 1/24: 1) and Cer (d18: 1/24: 1 (15Z)).
Claim 6 has similar issues for what is shown on Claim 1 above. The instant method in Claim 6 is drawn towards “treating,” and it is not claimed that one is determining if a treatment is effective or not, which is what the bottom part of the claim alludes to. Therefore, there is no claimed detecting, “if,” a treatment is effective or no.”. Therefore, it is suggested for clarity’s sake to amend the last section of claim 6 to be:
“and administering to the patient a dose of 0.03 g/kg/d of nervonic acid in the products containing nervonic acid,
wherein A2/A1 > 1.2 and B2/B1 > 1.3 is detected, and thereby the treatment of intaking the products containing nervonic acid is effective;
Claim Rejections - 35 USC § 103
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 non-obviousness.
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 & 5 is/are rejected under 35 U.S.C. 103 as being obvious by CHEN in CN113495160 & CN113495161 separately( Only sections from CN113495160 are cited below as the references teach substantially the same).
With respect to Claim 1, CHEN teaches of a method for diagnosing and treating cerebral disease and cognitive disorders(page 2, paragraph 1) with nervonic acid (abstract).
CHEN further teaches of detecting sphingomyelin (d17: 1/24: 1); and ceramide (d18: 1/24: 1(15Z)) as a marker, and further of using these markers to determine if there is a nervonic acid effect or not after treating with nervonic acid (abstract, Claim 2).
CHEN further teaches of using an ultra high performance liquid chromatography mass spectrometry for detection(Page 4,4 paragraphs from bottom starting with “if,).”
And further of using a C18 chromatographic column (2.1 * 10 0 mm, 1.7 μ m, Waters), mobile phase is 10 mM ammonium formate -0.1 % formic acid-acetonitrile (A, 6 0: 40, v/v) and 10 mM ammonium formate -0.1 % formic acid-isopropanol-acetonitrile (B, 90: 10, v/v) (Page 5, last paragraph & Page 6 first paragraph),
of detecting lipids in positive and negative two modes, collecting range is m/z50 ~ 1200 years, collecting time is for 0.2s/ the ion source temperature is 120 degrees centigrade; the desolvent temperature is 600 degrees centigrade; the gas flow is 1000L/h, the nitrogen is the flowing gas. the capillary voltage is 2.0kV (+) /cone voltage is 1.5kV (-); the cone voltage is 30V ((Page 5, last paragraph & Page 6 first paragraph), as instantly claimed.
CHEN teaches of detection after administration of a product containing nervonic acid (OT group) and in a placebo group (so before administration of nervonic acid(CK represents(Page 5, paragraph 2 & Page 6, paragraph 2 starting with “orthogonal”).
CHEN further teaches of administering a product with 0.03g/kg/d nervonic acid content (Page 5, paragraph 2, starting with “the 29..”).
CHEN further teaches of using the above methods to determine if the nervonic acid product treatment is effective or not and specifically of using ceramide d18: 1/24: 1 (15Z) and (d17: 1/24: 1) to determine if it is effective or not (abstract, page 3, paragraphs 2 & 4).
CHEN does not teach of specific detection of the 1.2 times or more and 1.3 times the detected concentration being “effective.” However, since CHEN teaches of detecting the exact same compounds claimed using the exact same method and the conditions and reagents claimed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize through routine experimentation to arrive at the claimed 1.2 time and 1.3 times. “[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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
With respect to Claim 5, CHEN teaches of a method for diagnosing and treating cerebral disease and cognitive disorders(page 2, paragraph 1) with nervonic acid (abstract) but that the methods can be applied to a clinical kit (Page 8, ).
CHEN further teaches of detecting/using sphingomyelin (d17: 1/24: 1); and ceramide (d18: 1/24: 1(15Z)) as a marker(abstract, Claim 2, 2nd to last paragraph from bottom).
CHEN also teaches of using a mobile phase is 10 mM ammonium formate -0.1 % formic acid-acetonitrile (A, 6 0: 40, v/v) and 10 mM ammonium formate -0.1 % formic acid-isopropanol-acetonitrile (B, 90: 10, v/v) (Page 5, last paragraph & Page 6 first paragraph).
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being obvious by CHEN in CN113495160 & CN113495161 separately (Only sections from CN113495160 are cited below as the references teach substantially the same) in view of TERLUK in Nervonic Acid Attenuates Accumulation of Very Long-Chain Fatty Acids and is a Potential Therapy for Adrenoleukodystrophy.
With respect to Claim 6, CHEN teaches of a method for diagnosing and treating cerebral disease and cognitive disorders(page 2, paragraph 1) with nervonic acid (abstract).
CHEN further teaches of detecting sphingomyelin (d17: 1/24: 1); and ceramide (d18: 1/24: 1(15Z)) as a marker, and further of using these markers to determine if there is a nervonic acid effect or not after treating with nervonic acid (abstract, Claim 2).
CHEN further teaches of using an ultra high performance liquid chromatography mass spectrometry for detection(Page 4,4 paragraphs from bottom starting with “if,).”
And further of using a C18 chromatographic column (2.1 * 10 0 mm, 1.7 μ m, Waters), mobile phase is 10 mM ammonium formate -0.1 % formic acid-acetonitrile (A, 6 0: 40, v/v) and 10 mM ammonium formate -0.1 % formic acid-isopropanol-acetonitrile (B, 90: 10, v/v) (Page 5, last paragraph & Page 6 first paragraph),
of detecting lipids in positive and negative two modes, collecting range is m/z50 ~ 1200 years, collecting time is for 0.2s/ the ion source temperature is 120 degrees centigrade; the de-solvent temperature is 600 degrees centigrade; the gas flow is 1000L/h, the nitrogen is the flowing gas. the capillary voltage is 2.0kV (+) /cone voltage is 1.5kV (-); the cone voltage is 30V ((Page 5, last paragraph & Page 6 first paragraph), as instantly claimed.
CHEN teaches of detection after administration of a product containing nervonic acid (OT group) and in a placebo group (so before administration of nervonic acid(CK represents(Page 5, paragraph 2 & Page 6, paragraph 2 starting with “orthogonal”).
CHEN further teaches of administering a product with 0.03g/kg/d nervonic acid content (Page 5, paragraph 2, starting with “the 29..”).
CHEN further teaches of using the above methods to determine if the nervonic acid is effective or not and specifically of using ceramide d18: 1/24: 1 (15Z) and (d17: 1/24: 1) to determine if it is effective or not (abstract, page 3, paragraphs 2 & 4).
CHEN does not teach of specific detection of the A2/A1 is greater than or equals to 1.2 times or B2/B1 is greater than or equal to1.3 times the detected concentration being “effective.” However, since CHEN teaches of detecting the exact same compounds claimed using the exact same method and the conditions and reagents claimed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize through routine experimentation to arrive at the claimed 1.2 time and 1.3 times. “[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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
CHEN does not teach of diagnosis in a patient with demyelinating disease.
TERLUK is used to remedy this. TERLUK teaches of a method of detecting Adrenoleukodystrophy (ALD) (a demyelinating disease) that is characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD (abstract). TERLUK further teaches that the disorder involves cognitive deficits and demyelinating disease (Page 1014, column 1, first paragraph 1).
TERLUK even further teaches of using nervonic acid to treat these conditions and that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production (abstract). It would have been obvious to one of ordinary skill in the art to use nervonic acid as is done in TERLUK to treat in the method of SCHATZ since nervonic acid is known to successfully alter biochemistry and have potential therapeutic affect for individuals with ALD (in which patients have demyelination and cognitive decline) and therefore in improve patient’s internal biochemistries functioning (TERLUK, abstract).
It would have been obvious to one of ordinary skill in the art to diagnose in a treatment, nervonic acid is acting of in a patient with a demyelinating disease as is in TERLUK in the method of CHEN due to the need in the art for finding a treatment that prevents demyelinating lesions (Page 1008, column 1, paragraph 2).
Claims 1 & 6 are rejected under 35 U.S.C. 103 as being unpatentable by INDRA in US 20180059127 in view of SCHATZ in US 20180238914 in view of TERLUK in Nervonic Acid Attenuates Accumulation of Very Long-Chain Fatty Acids and is a Potential Therapy for Adrenoleukodystrophy further in view of SARAFIAN in Objective Set of Criteria for Optimization of Sample Preparation Procedures for Ultra-High Throughput Untargeted Blood Plasma Lipid Profiling by Ultra Performance Liquid Chromatography−Mass Spectrometry.
With respect to Claim 1, INDRA teaches of a method of determining a lipid imbalance in a subject, which includes detection of a composition of lipids in a subject in comparison to a control and also a method of treating the subject based on this lipid imbalance (abstract). INDRA teaches of detecting ceramides (paragraph 0009-0013) and sphingomyelin (paragraph 0038, 0040) by mass spectrometry (paragraph 0061-0063) and more specifically by ultra high performance liquid chromatography mass spectrometry wherein
mobile phase A (60:40, v/v) acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid,
and mobile phase B (90:10:4, v/v/v) isopropanol:acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid (paragraph 0065, 0137-0138).
INDRA teaches that the flow rate was 0.5 mL/min and the injection volume was 5 μL. TOF MS acquisition time was 0.25 seconds, and MS/MS acquisition time was 0.1 seconds. The scan range was m/z 70-1700 for TOF MS and m/z 50-1700 for MS/MS. Source parameters included nebulizing gases GS1 at 45, GS2 at 50, curtain gas at 35, positive mode ion spray voltage 5500 V, negative mode ion spray voltage at −4500 V, declustering potential at 80 and −80 V, and at an ESI source operating temperature of 550° C (0137-0138)--- which is different operating conditions than what is claimed.
INDRA teaches of using nervonic acid (paragraph 0039), but not really as a treatment and only as part of a lipid class.
INDRA does not teach of the claimed specific lipid variants of ceramide and sphingomyelin being detected.
SCHATZ is used to remedy this and teaches of a method for diagnosing a cardiac disease in a subject based on determining the amounts of at least three lipid metabolite biomarkers and at least one further cardiac biomarker (abstract).
SCHATZ teaches that the lipid biomarkers that are detected are Sphingomyelin(d17:1/24:1) (paragraph 0130), and detecting Ceramide(d18:1/24:1) (paragraph 0051) and of detecting them in serum samples (paragraph 0057).
SCHATZ further teaches of using these biomarkers to determine if the subject is in need of therapy or treatment (paragraph 0596-0611), and further of assessing if the treatment is effective or not (paragraph 0657).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect the specific variants of lipids shown in SCHATZ in the method of INDRA since these biomarkers shown the advantage of being indicative of a disease (SCHATZ, paragraph 0550).
INDRA and SCHATZ do not teach of treating with and diagnosing acting of or using nervonic acid or that the disorder or diagnosis is for a cognitive disorder.
TERLUK is used to remedy this. TERLUK teaches of a method of detecting Adrenoleukodystrophy (ALD) (a demyelinating disease) that is characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD (abstract). TERLUK further teaches that the disorder involves cognitive deficits and demyelinating disease (Page 1014, column 1, first paragraph 1).
TERLUK even further teaches of using nervonic acid to treat these conditions and that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production (abstract). It would have been obvious to one of ordinary skill in the art to use nervonic acid as is done in TERLUK to treat in the method of SCHATZ since nervonic acid is known to successfully alter biochemistry and have potential therapeutic affect for individuals with ALD (in which patients have demyelination and cognitive decline) and therefore in improve patient’s internal biochemistries functioning (TERLUK, abstract).
TERLUK teaches of using nervonic acid in 5, 20, and 50uM concentrations and of treating cells with this and further of increasing the concentration of nervonic acid over days (Page 1008, column 2, paragraphs 2-3 & Figure 1-4). TERLUK further teaches of administering multiple days and doses of treatments (Page 1012, column 1, last paragraph). TERLUK further teaches of administering nervonic acid at a dose of approximately 23 mg/kg (which reads on .023 g/kg/d) for 30 days and also 6g/kg/d--- since TERLUK teaches that this is “approximately,” the does this makes the instantly claimed .03 g/kg dose obvious to adjust and to optimize through routine optimization (Page 1015, column 2, paragraph 2). See MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to diagnose the acting of, or using nervonic acid to treat as is done in TERLUK in the method of SCHATZ due to the advantage it has shown as being a safe and non toxic treatment and due to the advantage it has for improving energy metabolism (Page 1015, column 2, paragraph 1).
INDRA and SCHATZ and TERLUK teach of the invention as shown above, including the use of mass spectrometry liquid chromatography as shown for Claim 1. They do not teach of the use of ultra-high performance liquid chromatography mass spectrometry (UHPLC) specifically with all of the claimed operating parameters other than the mobile phases.
SARAFIAN is used to remedy this and teaches of methods of profiling lipids using UHLPC mass spectrometry (abstract and title). SARAFIAN further teaches of using capillary voltage of 2.5kV, and cone voltage of 30V a source temperature at 120 degrees Celsius, a desolvation temperature at 400 degrees Celsius, desolvation flow gas at 800 L/h, and cone gas flow at 20L/h(Page 5767, column 2, 2nd to last paragraph). Further- though SARAFIAN teaches again of many of the claimed analysis conditions, as it does not call out the specific flow rates claimed and desolvation temperature, it would have been obvious to one of ordinary skill in the art to adjust and to optimize through routine optimization (Page 1015, column 2, paragraph 2). See MPEP 2144.05
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use UHPLC mass spec as is done in SARAFIAN in the methods of INDRA, SCHATZ and TERLUK due to the advantage it offers with respect to shorter acquisition times for similar resolution to HPLC (Page 5766, column 1, paragraph 1).
INDRA, SCHATZ, TERLUK, and SARAFIAN do not teach of the claimed 1.2 times and 1.3 times levels indicating effectiveness/ that the nervonic acid is working, however they make this obvious since they show increase in these compounds being better diagnostically.
However, since INDRA, SCHATZ, TERLUK, and SARAFIAN teaches of detecting the exact same compounds claimed using the exact same method and the conditions and reagents claimed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize through routine experimentation to arrive at the claimed 1.2 time and 1.3 times. “[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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Further, the numbers 1.2 and 1.3 themselves are result effective variables so would be obvious to optimize through routine experimentation. See MPEP 2144.05 See MPEP 2144.05. See MPEP 2144.05 II.
With respect to Claim 6, INDRA teaches of a method of determining a lipid imbalance in a subject, which includes detection of a composition of lipids in a subject in comparison to a control and also a method of treating the subject based on this lipid imbalance (abstract). INDRA teaches of detecting ceramides (paragraph 0009-0013) and sphingomyelin (paragraph 0038, 0040) by mass spectrometry (paragraph 0061-0063) and more specifically by ultra high performance liquid chromatography mass spectrometry wherein
mobile phase A (60:40, v/v) acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid,
and mobile phase B (90:10:4, v/v/v) isopropanol:acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid (paragraph 0065, 0137-0138).
INDRA teaches that the flow rate was 0.5 mL/min and the injection volume was 5 μL. TOF MS acquisition time was 0.25 seconds, and MS/MS acquisition time was 0.1 seconds. The scan range was m/z 70-1700 for TOF MS and m/z 50-1700 for MS/MS. Source parameters included nebulizing gases GS1 at 45, GS2 at 50, curtain gas at 35, positive mode ion spray voltage 5500 V, negative mode ion spray voltage at −4500 V, declustering potential at 80 and −80 V, and at an ESI source operating temperature of 550° C (0137-0138)--- which is different operating conditions than what is claimed.
INDRA teaches of using nervonic acid (paragraph 0039), but not really as a treatment and only as part of a lipid class.
INDRA does not teach of the claimed specific lipid variants of ceramide and sphingomyelin being detected.
SCHATZ is used to remedy this and teaches of a method for diagnosing a cardiac disease in a subject based on determining the amounts of at least three lipid metabolite biomarkers and at least one further cardiac biomarker (abstract).
SCHATZ teaches that the lipid biomarkers that are detected are Sphingomyelin(d17:1/24:1) (paragraph 0130), and detecting Ceramide(d18:1/24:1) (paragraph 0051) and of detecting them in serum samples (paragraph 0057).
SCHATZ further teaches of using these biomarkers to determine if the subject is in need of therapy or treatment (paragraph 0596-0611), and further of assessing if the treatment is effective or not (paragraph 0657).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect the specific variants of lipids shown in SCHATZ in the method of INDRA since these biomarkers shown the advantage of bing indicative of a disease (SCHATZ, paragraph 0550).
INDRA and SCHATZ do not teach of treating with and diagnosing acting of or using nervonic acid or that the disorder or diagnosis is for a cognitive disorder.
TERLUK is used to remedy this. TERLUK teaches of a method of detecting Adrenoleukodystrophy (ALD) that is characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD (abstract). TERLUK further teaches that the disorder involves cognitive deficits and demyelinating disease (Page 1014, column 1, first paragraph 1).
TERLUK even further teaches of using nervonic acid to treat these conditions and that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production (abstract). It would have been obvious to one of ordinary skill in the art to use nervonic acid as is done in TERLUK to treat in the method of SCHATZ since nervonic acid is known to successfully alter biochemistry and have potential therapeutic affect for individuals with ALD (in which patients have demyelination and cognitive decline) and therefore in improve patient’s internal biochemistries functioning (TERLUK, abstract).
TERLUK teaches of using nervonic acid in 5, 20, and 50uM concentrations and of treating cells with this and further of increasing the concentration of nervonic acid over days (Page 1008, column 2, paragraphs 2-3 & Figure 1-4). TERLUK further teaches of administering multiple days and doses of treatments (Page 1012, column 1, last paragraph). TERLUK further teaches of administering nervonic acid at a dose of approximately 23 mg/kg (which reads on .023 g/kg/d) for 30 days and also 6g/kg/d--- since TERLUK teaches that this is “approximately,” the does this makes the instantly claimed .03 g/kg dose obvious to adjust and to optimize through routine optimization (Page 1015, column 2, paragraph 2). See MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to diagnose the acting of, or using nervonic acid to treat as is done in TERLUK in the method of SCHATZ due to the advantage it has shown as being a safe and non toxic treatment and due to the advantage it has for improving energy metabolism (Page 1015, column 2, paragraph 1).
INDRA and SCHATZ and TERLUK teach of the invention as shown above, including the use of mass spectrometry liquid chromatography as shown for Claim 1. They do not teach of the use of ultra-high performance liquid chromatography mass spectrometry (UHPLC) specifically with all of the claimed operating parameters other than the mobile phases.
SARAFIAN is used to remedy this and teaches of methods of profiling lipids using UHLPC mass spectrometry (abstract and title). SARAFIAN further teaches of using capillary voltage of 2.5kV, and cone voltage of 30V a source temperature at 120 degrees Celsius, a desolvation temperature at 400 degrees Celsius, desolvation flow gas at 800 L/h, and cone gas flow at 20L/h(Page 5767, column 2, 2nd to last paragraph). Further- though SARAFIAN teaches again of many of the claimed analysis conditions, as it does not call out the specific flow rates claimed and desolvation temperature, it would have been obvious to one of ordinary skill in the art to adjust and to optimize through routine optimization (Page 1015, column 2, paragraph 2). See MPEP 2144.05
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use UHPLC mass spec as is done in SARAFIAN in the methods of INDRA, SCHATZ and TERLUK due to the advantage it offers with respect to shorter acquisition times for similar resolution to HPLC (Page 5766, column 1, paragraph 1).
INDRA, SCHATZ, TERLUK, and SARAFIAN do not teach of the claimed 1.2 INDRA, SCHATZ, TERLUK, and SARAFIAN do not teach of the claimed 1.2 times and 1.3 times levels indicating effectiveness/ that the nervonic acid is working, however they make this obvious since they show increase in these compounds being better diagnostically.
However, since INDRA, SCHATZ, TERLUK, and SARAFIAN teaches of detecting the exact same compounds claimed using the exact same method and the conditions and reagents claimed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize through routine experimentation to arrive at the claimed 1.2 time and 1.3 times. “[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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Further, the numbers 1.2 and 1.3 themselves are result effective variables so would be obvious to optimize through routine experimentation. See MPEP 2144.05 See MPEP 2144.05. See MPEP 2144.05 II.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable by SCHATZ in US 20180238914 in view of INDRA in US 20180059127.
With respect to Claim 5, SCHATZ teaches of what is shown above for Claim 1, including the claimed lipids and further teaches of using a kit for the invention (paragraph 0595, 0652-0653, 0655). SCHATZ further teaches of detecting Sphingomyelin(d17:1/24:1) (paragraph 0130) and detecting Ceramide(d18:1/24:1) (paragraph 0051).
SCHATZ does not teach of the kit including the claimed 2 mobile phases.
INDRA teaches of a method of determining a lipid imbalance in a subject, which includes detection of a composition of lipids in a subject in comparison to a control and also a method of treating the subject based on this lipid imbalance (abstract). INDRA teaches of detecting ceramides (paragraph 0009-0013) and sphingomyelin (paragraph 0038, 0040) by mass spectrometry (paragraph 0061-0063) and more specifically by ultra high performance liquid chromatography mass spectrometry wherein
mobile phase A (60:40, v/v) acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid,
and mobile phase B (90:10:4, v/v/v) isopropanol:acetonitrile:water containing 10 mM ammonium formate with 0.1% formic acid (paragraph 0065, 0137-0138).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to combine the mobile phase reagents of INDRA in a kit with the compounds of SCHATZ due to the advantage this would have for simplifying lipid extraction and analysis (paragraph 0136-0137).
Response to Arguments
Applicant's arguments filed 03/31/2026 have been fully considered but they are not persuasive.
The prior 101 rejection is overcome, since the claims are now drawn specifically to a method for detecting or a method for treating, and not a natural correlation or abstract idea.
The instant amendments dated 08/31/2026 have a few clarity issues as noted in the 112b rejection above.
Applicant’s arguments with respect to claim(s) have been considered but are moot because the new ground of rejection does not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
With respect to the newly found prior art, the examiner notes that it is the best prior art found. For Claims 1, 5, & 6 there are two main 103 rejections made.
For Claims 1 & 6, the first is INDRA in view of SCHATZ in view of TERLUK and in further view of SARAFIAN. The examiner notes that this is a 4 reference 103, so if applicant is able to make reasonable arguments, it is possible that this could be overcome.
For Claim 5, it is SCHATZ in view of INDRA, as the claimed kit is so simple even outside of this teaching, the claimed kit seems reasonably easy to find teachings of in the prior art.
For claims 1, 5, & 6, the second main 103 rejection is made with respect to CHEN in CN113495160 & CN113495161, which are both pieces of prior art by the same inventor of the instant US application 12/021229 and for Claim 6, in view of Terluk. The CHEN documents CN113495160 & CN113495161 were published over a year before the effective filing date of the instant claims---the instant claims being filed 02/14/2023 with CN113495160 published 10/12/2021 and CN113495161 also published 10/12/2021. Therefore they are prior art, and they very substantially overlap with the instant claims. The examiner could not determine quickly if there is any significant disclosure in the instant invention which is not taught by the CHEN prior arts CN113495160 & CN113495161. If applicant can overcome the CHEN references, then they are more likely to overcome the other cited references as well.
With respect to the prior art, applicant argues In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, there is adequate reason to combined the references as shown in the art rejection above.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, applicant seems to be arguing moreso with respect to hindsight reasoning that the prior art references are non-analagous art. With respect to this, the examiner disagrees.
In response to applicant's argument that prirr art references is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, all prior art references are reasonably pertinent to the inventors problem which involves testing for lipids and treating with nervonic acid. The references do nor recite entirely different problems from what is instantly claimed nor are they in different fields of endeavour ( which is what applicant argues).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant also argues that the present specification demonstrates unexpected results in that the claimed two biomarkers provide an earlier diagnostic marker on if nervonic acid is effective or not. The examiner maintains that this is not unexpected, especially given the CHEN references shown above.
All claims remain rejected.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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