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 Final Office Action based on application 17/910700 response dated 12/18/2025.
Claims 1-2, 5, 13 & 52-54 have been examined, and fully considered.
Claims 3-4, 6-12,14-21, 24-25, 27, 32-51 are cancelled.
Claims 22-23, 26, & 28-31 are withdrawn.
Claims 52-54 was newly added.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5, 13 & 52-54 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11519899 in view of BAHADO-SINGH in US 20160377639.
With respect to Claims 1-2, 5, 13 & 52-54, U.S. Patent No. 11519899 teach of A method of diagnosing mild traumatic brain injury (mTBI) in a subject comprising: (a) obtaining a metabolite profile from the subject; (b) using machine learning to compare the subject's profile with a predetermined set of metabolite profiles of mTBI and a predetermined set of metabolite profiles of non-mTBI (referred to as “control” or “normal”) to determine if the subject has mTBI, the predetermined set of metabolite profiles of mTBI and non-mTBI comprise metabolites selected from: C0, C14:1, C14:2, C16, C18, C18:1, C18:2, C2, C3, C4, C5, C5-OH (C3-DC-M), C9, lysoPC a C16:0, lysoPC a C16:1, lysoPC a C17:0, lysoPC a C18:0, lysoPC a C18:1, lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4, lysoPC a C26:0, lysoPC a C26:1, lysoPC a C28:0, lysoPC a C28:1, PC aa C24:0, PC aa C28:1, PC aa C30:0, PC aa C30:2, PC aa C32:0, PC aa C32:1, PC aa C32:2, PC aa C32:3, PC aa C34:1, PC aa C34:2, PC aa C34:3, PC aa C34:4, PC aa C36:0, PC aa C36:1, PC aa C36:2, PC aa C36:3, PC aa C36:4, PC aa C36:5, PC aa C36:6, PC aa C38:0, PC aa C38:1, PC aa C38:3, PC aa C38:4, PC aa C38:5, PC aa C38:6, PC aa C40:2, PC aa C40:3, PC aa C40:4, PC aa C40:5, PC aa C40:6, PC aa C42:0, PC aa C42:1, PC aa C42:4, PC aa C42:5, PC aa C42:6, PC ae C30:0, PC ae C30:1, PC ae C32:1, PC ae C32:2, PC ae C34:0, PC ae C34:1, PC ae C34:2, PC ae C34:3, PC ae C36:0, PC ae C36:1, PC ae C36:2, PC ae C36:3, PC ae C36:4, PC ae C36:5, PC ae C38:0, PC ae C38:1, PC ae C38:2, PC ae C38:3, PC ae C38:4, PC ae C38:5, PC ae C38:6, PC ae C40:1, PC ae C40:2, PC ae C40:3, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:2, PC ae C42:3, PC ae C42:4, PC ae C42:5, PC ae C44:3, PC ae C44:4, PC ae C44:5, PC ae C44:6, SM (OH) C14:1, SM (OH) C16:1, SM (OH) C22:1, SM (OH) C22:2, SM (OH) C24:1, SM C16:0, SM C16:1, SM C18:0, SM C18:1, SM C20:2, SM C22:3, SM C24:0, SM C24:1, SM C26:0, SM C26:1, H1, Alanine, Arginine, Asparagine, Citrulline, Glutamine, Glutamic acid, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine, Acetyl-Ornithine, Asymmetricdimethylarginine, Total Dimethylarginine, alpha-Aminoadipic acid, Creatinine, Kynurenine, Methionine-Sulfoxide, trans-OH-Proline, Putrescine, Spermine, Taurine, 2-Hydroxybutyrate, 3-Hydroxybutyrate, 3-Hydroxyisovalerate, Acetate, Acetone, Betaine, Carnitine, Citrate, Creatine, Formate, Glucose, Glutamine, Glycerol, Lactate, Methanol, Propylene glycol, Pyruvate, and Succinate, and wherein the predetermined set of metabolite profiles of mTBI and non-mTBI include at least one phosphatidylcholine having one acyl- and one alkyl-bound fatty acids (PC ae); and (c) determining whether the subject is positive or negative for mTBI based on said comparison (abstract).
U.S. Patent No. 11519899 does not teach of the claimed treatment specifically with respect to decreased levels.
BAHADO-SINGH teaches of methods for detecting, diagnosing and/or treating traumatic brain injury (TBI) by detecting in a biological sample from a patient the levels of one or more of the metabolites: methionine sulfoxide, PC aa C 34:4, ATP, AMP, NAD+, ADP, IMP, spermidine, lysoPC a C20:3, C18:1, and proline. In some embodiments, the method also includes diagnosing the patient with traumatic brain injury when the one or more metabolites in the biological sample is at a different level than a statistically validated threshold for the one or more metabolites, and CT, MRI, or PET indicates traumatic brain injury to the brain of the patient. In further embodiments, once traumatic brain injury is diagnosed, the patient is treated for the traumatic brain injury (abstract).
BAHADO-SINGH further teaches of the TBI being a mild TBI from causes such as concussions (paragraph 0003-0005), and diagnosing to mild, moderate or severe stages of TBI (paragraph 0042, 0094, 0103).
The diagnosis for the mild TBI can include obtaining a biological sample and measuring the level of lipid PC aa C 34:3 and some other similar lipids, and of detecting the levels of these lipids by liquid chromatography tandem mass spectrometry (Tables, 4, 5).
For the detection, 10 samples with TBI are compared to 8 controls (paragraph 0148), and it is shown that the level of PC aa C 34:3, is decreased indicated by the down arrow compared to the control (Tables 4, 5).
BAHADO-SINGH even further teaches of treating the patient if the biological sample measures a level that is different than a statistically validated threshold comparison when compared to a control (abstract, paragraphs 0102-01014, 0090). Further, BAHDO-SINGH teaches of looking for both reduced levels or elevated levels of the metabolites compared to the statistically validated threshold control (paragraph 0095). Again- BAHDO SINGH teaches of detection of levels of PC aa C 34:3 being decreased in TBI patient when compared to a control (Tables 4 & 5).
It would have been obvious to one of ordinary skill in the art to treat based on noticing a decreased or increased level of biomarkers as is done in BAHDO- SINGH in the method of FRASER due to the advantage this offers for ameliorating the disease or disorder (BAHDO-SINGH, paragraph 0044).
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 ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1-2, 5, 13 & 52-53 are directed to non-statutory subject matter.
The invention of instant claims is drawn towards a method of diagnosing mild traumatic brain injury (mTBI). However, as instantly considered as a whole the claim is drawn towards the judicial exceptions which are a combination of a natural correlation and abstract idea without significantly more to make the claims move past these judicial exceptions.
Through 101, inquiry:
Inquiry: Are the claims directed to a statutory category of invention?
Yes, independent Claims 1 & 54 and all claims depending therefrom are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Yes, independent Claim 1 and those that depend therefrom are drawn towards “diagnosing,” a mild traumatic brain injury (mTBI) which is a concussion. This is done by obtaining a sample from a subject an comparing a level of one or more lipid species (as claimed) to a normal control sample. The claimed diagnosing on the basis of level of biomarker (on of the biomarkers claimed in Claim 1) compared to a normal level of biomarker is a natural correlation. This is a law of nature judicial exception. See USPTO subject matter eligibility example 29.
Further, as instantly claimed, the diagnosing is done by “comparing,” and it is noted that no actual measurement or detection occurs, nor are the claims drawn towards measurement or detection. “Comparing,” as claimed is a mental process, which can be performed in the human mind, and is another type of judicial exception of an abstract idea. This remains the case when the very generally claimed, “machine learning,” as claimed is used for the comparing.
See MPEP 2106.03 & 2106.04.
Independent Claim 54, is drawn towards a method of treating. It is noted that this claim since it is drawn towards a method of treating and there are no instances where treatment does not occur, is not rejected under 101. Therefore, there is no further analysis for Claim 54.
Step 2A, Prong 2: Has the natural correlation or abstract idea been integrated into a particular practical application?
In Claim 1, there is no particular practical application.
The following steps are required for Claim 1:
Obtaining a test sample
Comparing the level of lipid/s of those claimed to the level/s in a normal control sample, using quantitative measurements and machine learning.
For obtaining a test sample, for the claimed method—this is considered insignificant extra solution activity performed to accomplish the judicial exception. There is no derivatization of the sample or anything else claimed which changes it from its natural state, nor which makes it more that something which is observe (a data pull) to accomplish the judicial exception. Therefore, this does not integrate the judicial exception into a practical application. See MPEP 2106.04 (d) I. & MPEP 2106.05 (g) for insignificant extra-solution activity.
For comparing the level of lipid/s of those claimed to the level/s in a normal control sample, again it is noted that this comparison is an abstract idea itself and therefore does not practically apply itself. Using quantitative measurement is just a general measurement which is doing a data pull to accomplish the claimed judicial exceptions and therefore is insignificant extra-solution activity. See MPEP 2106.05 (g).
Further the use in the claim of “using,” “machine learning,” as generally claimed remains an abstract idea as it isn’t stated in any detail how machine learning, a computer process, is performed in any way in which makes a technological improvement. Though not claimed, machine learning, must be done by a computer or machine. As claimed, it is only used for the claimed comparison which is a process which can be performed in the human mind, so this equates at the level of generality claimed as performing a mental process (comparison) on a generic computer or in a computer environment. See MPEP 2106.04 (a) (2), III. Mental Processes, C. 1-3.
Therefore, nothing in Claim 1 practically applies the judicial exceptions.
Step 2B: Do the claims recite any elements which are significantly more than the natural correlation or abstract idea?
The following steps are required for Claim 1:
Obtaining a test sample
Comparing the level of lipid/s of those claimed to the level/s in a normal control sample using quantitative measurement and machine learning.
All of the above steps including obtaining test samples and comparing to normal levels for analysis and diagnosis, and treating the subject if there is a decrease compared to normal, are well understood, routine and conventional (WURC) in the art. There is nothing claimed which requires the claimed biomarkers to be derivatized or processed in any way which is not WURC, and further no unconventional way of performing a comparison nor an unconventional treatment is claimed. Further, quantitatively measuring and using very basic machine learning to do no more than compare, is WURC. Therefore, this is standard laboratory technique and is not sufficient to show an improvement in technology or add significantly more. See MPEP 2106.05 (a) & MPEP 2106.05 (d).
The dependent claims are reviewed for additional limitations dependent on the independent claim above.
Claim 2 specifies that when the lipid levels increase over time the subject is normalizing/getting better. This is part of the natural correlation (diagnosis) judicial exception and therefore does not practically apply at step 2 A/2 nor does it add significantly more at step 2B.
Claim 5 specifies that the normal control is obtained from a subject at baseline. This is part of the natural correlation (diagnosis) judicial exception itself still and therefore does not practically apply at step 2 A/2 nor does it add significantly more at step 2B.
Claim 13 specifies that the same is a body fluid sample. This is part of the natural correlation (diagnosis) judicial exception (biomarker in natural sample correlation with disease) and therefore does not practically apply at step 2 A/2 nor does it add significantly more at step 2B.
Claim 52 does not change the matters above. Claim 52 specifies that a PC is administered if the subject is diagnosed. However, this is only, “if,” which means the claims are left open to instances where no treatment occurs. Therefore, there is no practical application nor is there significantly more in this instance.
Claim 53 specifies that the machine learning is used for comparison of a single or multiple lipids. As claimed the “machine learning,” still is just a simple comparison and is not showing any improvement in technology. Therefore- this is analyzed the same as the machine learning in Claim 1 and does not change matters.
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.
Claim 1-2, 5, 13 & 52-54 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.
The term “significant” in claims 1 & 54 is a relative term which renders the claim indefinite. The term “significant” 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. Specifically one person would think a significant decrease is different from another person, therefore this is a relative term.
Claims 2, 5, 13 & 52-53 are rejected by virtue of being dependent on Claim 1.
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 nonobviousness.
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.
Claims 1-2, 5, 13 & 53 are rejected under 35 U.S.C. 103 as being unpatentable by BAHADO-SINGH in US 20160377639 in view of FRASER in US 20180074038.
With respect to Claim 1, BAHADO-SINGH teaches of methods for detecting, diagnosing and/or treating traumatic brain injury (TBI) by detecting in a biological sample from a patient the levels of one or more of the metabolites: methionine sulfoxide, PC aa C 34:4, ATP, AMP, NAD+, ADP, IMP, spermidine, lysoPC a C20:3, C18:1, and proline. In some embodiments, the method also includes diagnosing the patient with traumatic brain injury when the one or more metabolites in the biological sample is at a different level than a statistically validated threshold for the one or more metabolites, and CT, MRI, or PET indicates traumatic brain injury to the brain of the patient. In further embodiments, once traumatic brain injury is diagnosed, the patient is treated for the traumatic brain injury (abstract).
BAHADO-SINGH teaches of the TBI being a mild TBI from causes such as concussions (paragraph 0003-0005), and diagnosing to mild, moderate or severe stages of TBI (paragraph 0042, 0094, 0103). BAHADO-SINGH further teaches of comparing the levels of PC aa C 42:6, PC ae C 36:0, PC aa C 32:0 and PC ae C 36:2 (Tables 4 & 5) and further of diagnosing to mild, moderate or severe stages of TBI (paragraph 0042, 0094, 0103). Specifically, BAHADO-SINGH teaches of PC ae C 36:0 being significantly decreased in TBI patients in comparison to the Sham control (See table 4 and table 5, paragraph 0011-0012).
The diagnosis for the mild TBI can include obtaining a biological sample and measuring the level of lipid PC aa C 34:3 and some other similar lipids, and of detecting the levels of these lipids by liquid chromatography tandem mass spectrometry (Tables, 4, 5).
For the detection, 10 samples with TBI are compared to 8 controls (paragraph 0148), and it is shown that the level of PC aa C 34:3, is decreased indicated by the down arrow compared to the control (Tables 4, 5).
BAHADO-SINGH even further teaches of treating the patient if the biological sample measures a level that is different than a statistically validated threshold comparison when compared to a control (abstract, paragraphs 0102-01014, 0090). Further, BAHDO-SINGH teaches of looking for both reduced levels or elevated levels of the metabolites compared to the statistically validated threshold control (paragraph 0095). Again- BAHDO SINGH teaches of detection of levels of PC aa C 34:3 being decreased in TBI patient when compared to a control (Tables 4 & 5).
BAHADO-SINGH does not teach of performing the comparison using generalized machine learning. FRASER is used to remedy this.
FRASER teaches of methods of diagnosing central nervous system injuries such as acquired brain injury (ABI) and/or acquired spinal cord injury (ASI), including mild TBI (concussion or blast wave), mild ASI (contusion, stretch or partial cord transection), non-TBI brain injury and/or non-TSI spinal cord injury in a subject (animal or human). The method includes (a) obtaining a biological test sample from the subject, identifying metabolites in the subject's sample using metabolomics thereby obtaining a subject's metabolite matrix and generating a subject's profile using the patient's metabolite matrix; and (b) using multivariate statistical analysis and machine learning to compare the subject's profile with predetermined set of profiles of CNS injuries and a predetermined set of profiles of controls to determine if the subject has a CNS injury (abstract).
FRASER further teaches of the TBI being a mild TBI from causes such as concussions (paragraph 0003-0005), and diagnosing to mild, moderate or severe stages of TBI (paragraph 0005).
The diagnosis for the mild TBI can include obtaining a biological sample and measuring the level of lipid PC aa C 34:3 and some other similar lipids, and of detecting the levels of these lipids by liquid chromatography tandem mass spectrometry (paragraphs 0030-0031, 0023). FRASER teaches that the metabolite profiles include measuring of PC ae C36:0(paragraph 0030-0031).
FRASER even further teaches of treating the patient (paragraph 0114), and even further teaches of using machine learning for comparison of the subjects profile with a predetermined set of profiles (abstract, paragraph, 0011, 0017, 0038, 0048, 0081, 0084, 0085, 0086, 0088, 0089). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use machine learning for the comparison as is done in the method of FRASER in the method of BAHADO-SINGH due to the advantage it offers with respect to high sensitivity for concussion diagnostics (FRASER, paragraph 0113).
With respect to Claim 2, BAHADO-SINGH teaches of monitoring injury progression and monitoring progress of the patient’s traumatic brain injury and recovery (paragraph 0060-0061).
With respect to Claim 5, BAHADO-SINGH teaches of comparison to a control that does not have TBI (paragraph 0095). BAHADO-SINGH further teaches of assessing a patient before and after treatment, so the first or second measurement could be considered a “reference normal control sample…obtained from the subject at baseline,” (paragraph 0106).
With respect to Claim 13, BAHADO-SINGH teaches of the sample being blood or serum samples (paragraph 0016-0018) or of being things like tears or sweat (paragraph 0041).
With respect to Claim 53, BAHADO-SINGH teaches of the invention as shown above but does not teach of performing the comparison using generalized machine learning to compare the level of the single or multiple lipids during recovery and medical intervention. FRASER is used to remedy this.
FRASER teaches of methods of diagnosing central nervous system injuries such as acquired brain injury (ABI) and/or acquired spinal cord injury (ASI), including mild TBI (concussion or blast wave), mild ASI (contusion, stretch or partial cord transection), non-TBI brain injury and/or non-TSI spinal cord injury in a subject (animal or human). The method includes (a) obtaining a biological test sample from the subject, identifying metabolites in the subject's sample using metabolomics thereby obtaining a subject's metabolite matrix and generating a subject's profile using the patient's metabolite matrix; and (b) using multivariate statistical analysis and machine learning to compare the subject's profile with predetermined set of profiles of CNS injuries and a predetermined set of profiles of controls to determine if the subject has a CNS injury (abstract).
FRASER further teaches of the TBI being a mild TBI from causes such as concussions (paragraph 0003-0005), and diagnosing to mild, moderate or severe stages of TBI (paragraph 0005).
The diagnosis for the mild TBI can include obtaining a biological sample and measuring the level of lipid PC aa C 34:3 and some other similar lipids, and of detecting the levels of these lipids by liquid chromatography tandem mass spectrometry (paragraphs 0030-0031, 0023). FRASER teaches that the metabolite profiles include measuring of PC ae C36:0(paragraph 0030-0031).
FRASER even further teaches of treating the patient (so the patient is undergoing recovery and medical intervention) (paragraph 0114), and even further teaches of using machine learning for comparison of the subjects profile with a predetermined set of profiles (abstract, paragraph, 0011, 0017, 0038, 0048, 0081, 0084, 0085, 0086, 0088, 0089). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use machine learning for the comparison as is done in the method of FRASER in the method of BAHADO-SINGH due to the advantage it offers with respect to high sensitivity for concussion diagnostics (FRASER, paragraph 0113).
Claims 52 & 54 are rejected under 35 U.S.C. 103 as being unpatentable by BAHADO-SINGH in US 20160377639 in view of FRASER in US 20180074038 and further in view of ZUCHMAN in Brain Phospholipid Precursors Administered Post-Injury Reduce Tissue Damage and Improve Neurological Outcome in Experimental Brain Injury and further in view of LICHTENBERGER in US 20110065677.
With respect to Claims 52 & 54, BAHADO-SINGH teaches of methods for detecting, diagnosing and/or treating traumatic brain injury (TBI) by detecting in a biological sample from a patient the levels of one or more of the metabolites: methionine sulfoxide, PC aa C 34:4, ATP, AMP, NAD+, ADP, IMP, spermidine, lysoPC a C20:3, C18:1, and proline. In some embodiments, the method also includes diagnosing the patient with traumatic brain injury when the one or more metabolites in the biological sample is at a different level than a statistically validated threshold for the one or more metabolites, and CT, MRI, or PET indicates traumatic brain injury to the brain of the patient. In further embodiments, once traumatic brain injury is diagnosed, the patient is treated for the traumatic brain injury (abstract).
BAHADO-SINGH teaches of the TBI being a mild TBI from causes such as concussions (paragraph 0003-0005), and diagnosing to mild, moderate or severe stages of TBI (paragraph 0042, 0094, 0103). BAHADO-SINGH further teaches of comparing the levels of PC aa C 42:6, PC ae C 36:0, PC aa C 32:0 and PC ae C 36:2 (Tables 4 & 5) and further of diagnosing to mild, moderate or severe stages of TBI (paragraph 0042, 0094, 0103). Specifically, BAHADO-SINGH teaches of PC ae C 36:0 being significantly decreased in TBI patients in comparison to the Sham control (See table 4 and table 5, paragraph 0011-0012).
The diagnosis for the mild TBI can include obtaining a biological sample and measuring the level of lipid PC aa C 34:3 and some other similar lipids, and of detecting the levels of these lipids by liquid chromatography tandem mass spectrometry (Tables, 4, 5).
For the detection, 10 samples with TBI are compared to 8 controls (paragraph 0148), and it is shown that the level of PC aa C 34:3, is decreased indicated by the down arrow compared to the control (Tables 4, 5).
BAHADO-SINGH even further teaches of treating the patient if the biological sample measures a level that is different than a statistically validated threshold comparison when compared to a control (abstract, paragraphs 0102-01014, 0090). Further, BAHDO-SINGH teaches of looking for both reduced levels or elevated levels of the metabolites compared to the statistically validated threshold control (paragraph 0095). Again- BAHDO SINGH teaches of detection of levels of PC aa C 34:3 being decreased in TBI patient when compared to a control (Tables 4 & 5).
FRASER further teaches of the invention as shown above for Claim 1.
BAHADO-SINGH and FRASER do not teach of treatment with one of the claimed PCs.
ZUCHMAN is used to remedy this and teaches of administration of phospholipid precursors to traumatic brain injury patients (abstract). Specifically, ZUCHMAN teaches of the compounds which are administered in a diet to include phosphatidylcholines (PCs) and phosphatidylethanolamines being some of these precursor compounds (Page 25, column 2, paragraph 2), and of administering soy lecithine which is shown to contain posphatidylcholines and phosphatidyethanolamines (Page 27, Table 1,5 lines from bottom and down) by way of a multi-nutrient called Fortasyn Connect.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to administer the phosphatidylcholine compounds multi-nutrient as is done in ZUCHMAN in the methods of BAHADO-SINGH and FRASER due to the advantage that this nutrient has shown with other related patients such as dementia and due to the great potential it has in treating TBIs (abstract).
ZUCHMAN does not teach of the phosphatidylcholines which are used for treatment being specifically the claimed ones which are PC ae C36:0 or PC ae C36:2 or PC aa C32:0.
LICHTENBERGER is used to remedy this and teaches of methods for treating inflammation (this is also present in TBI), with compositions comprising lecithin oils and soy lechithin (abstract, paragraph 0155, 0158). More specifically, LICHTENBERGER teaches that the phospholipids used in the invention can be dipalmitophosphatidylcholine, which is another name for PC aa C32:0 (paragraph 0145), and that the phospholipids are used as a non-aqueous carrier with an NSAID for treating inflammation (Claim 1).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use the phospholipid composition as is done in LICHTENBERGER and administering it to a patient to treat inflammation as is done in LICHTENBERGER, in the methods of ZUCHMAN, FRASER, and BAHADO-SINGH due to the advantage the phospholipid compound/adding a phospholipid to a treating compounds offers for providing low gastrointestinal toxicity and enhanced therapeutic activity (LICHTENBERGER, abstract).
Response to Arguments
Applicant's arguments filed 12/18/2025 have been fully considered but they are not persuasive.
With respect to the double patenting rejection, it is maintained for this time, but will be re-reviewed if the application approaches allowance.
With respect to the 101 rejection, it is maintained for the significantly amended claims, as shown in the above rejection. Since independent Claim 1 has been significantly amended, this is addressed in the rejection above, instead of in the response to arguments. It is noted that new claim 54 is not rejected under 101.
Also, 112 rejections were added to the record above, due to amendments made 12/18/2025.
The 102 rejection has been overcome due to amendments made 12/18/2025, however 103 rejections remain as shown above.
Applicant argues about the 103 rejection FRASER in view of BAHDO-SINGH. This is not longer the rejection made, since due to the amendments BAHDO-SINGH is view of FRASER is found to be the best rejection. Therefore, applicant does not argue about the references in the order and based on the grounds of rejection currently used, since due to amendments dated 12/18/2025, the order was changed.
With respect to BADHO-SINGH, applicant argues that the instant invention only relates to “significant,” decrease and that BAHDO-SINGH does not teach of this. With respect to this, the examine disagrees, as significant is a relative term which can mean different things to different people. This is noted in the 112 rejection above.
With respect to FRASER, applicant argues that FRASER does not teach of the claimed PC compounds with an up or down arrow to indicate increase or decrease. The examiner notes that the BAHDO-SINGH reference, which is the primary reference teaches of this.
Therefore, the examiner disagrees with applicant’s arguments about the prior art.
All claims remain rejected.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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