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 18/014582 election response filed 12/05/2025.
Claims 1-12 & 14-16 are pending.
Claims 1-5 have been elected and have been fully considered.
Election/Restrictions
Applicant’s election without traverse of Group I, Claims 1-5 in the reply filed on 12/05/2025 is acknowledged.
Claim 6-12 & 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/05/2025.
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over ANCSIN in US 20180179574 in view of GIMENO in US 20050054022.
With respect to Claim 1, ANCSIN teaches of a method for characterization of hypertriglyceridemia (HTG) in a subject. In particular, systems and methods, are provided for identifying the specific deficiency(ies) leading to HTG (abstract).
More specifically with respect to what is claimed, ANCSIN teaches of determining/assessing the TG (triglyceride) capacity/clearance pathway of the subject (paragraph 0043) and that if impaired triglyceride capacity is detected, it is a risk factor for metabolic syndrome (paragraph 0003)--- so the triglyceride capacity can be considered triglyceride metabolic capacity, as claimed, through broadest reasonable interpretation.
With respect to Claim 1, it is noted that the “acquiring a value,” “relating to,” “ a triglyceride metabolic capacity,” is interpreted as just “ a measured fluorescence intensity that is derived from the fluorescent label and the leucocytes,” as claimed in Claim 1, second step.
ANCSIN teaches that the determination of triglyceride capacity is accomplished by using routine blood samples from patients and including assessing the endogenous lipoprotein lipase activity of blood leukocytes (white blood cells) to determine the specific deficiency causing the HTG (paragraph 0005).
This is done by (a) exposing a blood sample (which includes leukocytes) from the subject to a triglyceride substrate, wherein the triglyceride substrate undergoes a detectable change in fluorescence upon hydrolysis by LpL. The triglyceride substrate in this context just means triglyceride modified with a fluorophore to form a fluorogenic triglyceride substrate (e.g., a triglyceride analog having a terminal fluorophore on one or more fatty acid chains of the triglyceride) (paragraphs 0006-0007).
This blood sample containing the leukocytes with mixed with the fluorogenic substrate reads on the claimed, “first step of mixing,” and “thus bringing the fatty acid labeled with the fluorescent substance,” (triglyceride substate which has one or more fatty acids, labeled with fluorophore) “into contact with the leucocytes,” by mixing into a mixture (paragraph 0022-0023).
ANCSIN further teaches of acquiring a detectable increase in fluorescence/fluorescence intensity signal (value) upon hydrolysis from LpL (paragraph 0007, 0045, 0056), and thereby acquiring, “a value relating to the triglyceride metabolic capacity,” through broadest reasonable interpretation.
ANCSIN even further teaches that the fatty acids in the fluorogenic-TG (triglyceride) substrate can be one or more fatty acids (paragraphs 0044-0045).
Instant Claim 1 also requires that the fatty acid compound contains a fatty acid residue, the fatty acid residue has 8 to 26 carbons, and a part of hydrogen atoms constituting the fatty acid residue, excluding a terminal methyl group of the fatty acid residue may be substituted by and alkyl group having 1 to 3 carbon atoms. ANCSIN do not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having this structure.
GIMENO is used to remedy this. GIMENO further teaches of a method of using labeled fatty acids to detect compounds. This is analogous art to what the ANCSIN reference is doing by labeling the fatty acid component of triglycerides, to detect compounds in leucocytes.
Specifically, GIMENO teaches that a fatty acid labeled with BODIPY is used, and even more specifically that the compound which is used is BODIPY-fatty acid (4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid) (paragraph 0083, 0149). Of the fluorescent labeled fatty acid, 4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid, the dodecanoic acid is the fatty acid. The formula for dodecanoic acid is C11H23COOH and it has 12 total carbons, 10 of which are in the fatty acid residue chain, so this reads on the instantly claimed 8 to 26 carbons and “a part of hydrogen atoms”. Dedecanoic acid also has a terminal methyl group, as another way to write it’s formula is CH3-(CH2)10-COOH. CH3 is the terminal methyl group. The claim limitation- “may,” “be substituted by an alkyl group having 1 to 3 carbon atoms,” is optional due to the, “may,” so this is not required by the claim.
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 fluorescent label/fatty acid pair as done in GIMENO having the claimed structure in the method of ANCSIN due to the advantage this fatty-acid/fluorescent label has in giving measurable fluorescence and due to the advantage it offers for being able to flag uptake in cells (such as the leukocytes of ANSCIN)(GIMENO, paragraph 0073, 0149, 0082-0083).
Claim(s) 2-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over ANCSIN in US 20180179574 in view of GIMENO in US 20050054022 and further in view of GOODMAN in New Myocardial Imaging Agents: Synthesis of 15-(p-Iodophenyl)-3(.R,iS)-methylpentadecanoic Acid by Decomposition of a 3,3-(l,5-Pentanediyl)triazene Precursor (as cited on IDS dated 03/10/2023).
With respect to Claim 2, ANCSIN and GIMENO teach of the claimed invention as shown above for Claim 1. They do not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having the structure of claim 2 with a substituted or unsubstituted phenyl group on the terminal methyl group of the fatty acid
GOODMAN is used to remedy this. GOODMAN teach using methyl-branched long-chain fatty acids such as 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (has a phenyl of terminal methyl group of the pentadecanoic acid, fatty acid) are of interest as imaging/labeling agents (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the fatty acid of GOODMAN as the fatty acid part of the fluorophore-fatty acid label in ANCSIN and GIMENO due to the advantage that this fatty acid has shown in having a pronounced uptake, which therefore gives better detection signal (GOODMAN, abstract).
With respect to Claim 3, ANCSIN and GIMENO teach of the claimed invention as shown above for Claim 1. They do not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having the structure of claim 2 with a substituted or unsubstituted phenyl group on the terminal methyl group of the fatty acid
GOODMAN is used to remedy this. GOODMAN teach using methyl-branched long-chain fatty acids such as 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (has a phenyl of terminal group of the pentadecanoic acid, fatty acid) are of interest as imaging/labeling agents (abstract). 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid has the “general,” formula as claimed in instant Claim 3.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the fatty acid of GOODMAN as the fatty acid part of the fluorophore-fatty acid label in ANCSIN and GIMENO due to the advantage that this fatty acid has shown in having a pronounced uptake, which therefore gives better detection signal (GOODMAN, abstract).
With respect to Claim 4, ANCSIN teaches of determining/assessing the TG (triglyceride) capacity/clearance pathway of the subject (paragraph 0043) and that if impaired triglyceride capacity is detected, it is a risk factor for metabolic syndrome (paragraph 0003)--- so the triglyceride capacity can be considered triglyceride metabolic capacity, as claimed, through broadest reasonable interpretation.
ANCSIN teaches that this determination of triglyceride capacity is accomplished by using routine blood samples from patients and including assessing the endogenous lipoprotein lipase activity of blood leukocytes (white blood cells) to determine the specific deficiency causing the HTG (paragraph 0005).
This is done by (a) exposing a blood sample (which includes leukocytes) from the subject to a triglyceride substrate, wherein the triglyceride substrate undergoes a detectable change in fluorescence upon hydrolysis by LpL. The triglyceride substrate in this context just means triglyceride modified with a fluorophore to form a fluorogenic triglyceride substrate (e.g., a triglyceride analog having a terminal fluorophore on one or more fatty acid chains of the triglyceride) (paragraphs 0006-0007). ANSCIN teaches that the triglyceride/fatty acid is linked to the fluorophore using a linker (paragraph 0045).
This blood sample containing the leukocytes with mixed with the fluorogenic substrate reads on the claimed, “first step of mixing,” and “thus bringing the fatty acid labeled with the fluorescent substance,” (triglyceride substate which has one or more fatty acids, labeled with fluorophore) “into contact with the leucocytes,” by mixing into a mixture (paragraph 0022-0023).
ANCSIN further teaches of acquiring a detectable increase in fluorescence/fluorescence intensity signal (value) upon hydrolysis from LpL (paragraph 0007, 0045, 0056), and thereby acquiring, “a value relating to the triglyceride metabolic capacity,” through broadest reasonable interpretation.
ANCSIN even further teaches that the fatty acids in the fluorogenic-TG (triglyceride) substrate can be one or more fatty acids (paragraphs 0044-0045).
Instant Claim 1 also requires that the fatty acid compound contains a fatty acid residue, the fatty acid residue has 8 to 26 carbons, and a part of hydrogen atoms constituting the fatty acid residue, excluding a terminal methyl group of the fatty acid residue may be substituted by and alkyl group having 1 to 3 carbon atoms. ANCSIN do not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having this structure.
GIMENO is used to remedy this. GIMENO further teaches of a method of using labeled fatty acids to detect compounds. This is analogous art to what the ANCSIN reference is doing by labeling the fatty acid component of triglycerides, to detect compounds in leucocytes.
Specifically, GIMENO teaches that a fatty acid labeled with BODIPY is used, and even more specifically that the compound which is used is BODIPY-fatty acid (4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid) (paragraph 0083, 0149). Of the fluorescent labeled fatty acid, 4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid, the dodecanoic acid is the fatty acid. The formula for dodecanoic acid is C11H23COOH and it has 12 total carbons, 10 of which are in the fatty acid residue chain, so this reads on the instantly claimed 8 to 26 carbons and “a part of hydrogen atoms”. Dedecanoic acid also has a terminal methyl group, as another way to write it’s formula is CH3-(CH2)10-COOH. CH3 is the terminal methyl group. The claim limitation- “may,” “be substituted by an alkyl group having 1 to 3 carbon atoms,” is optional due to the, “may,” so this is not required by the claim.
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 fluorescent label/fatty acid pair as done in GIMENO having the claimed structure in the method of ANCSIN due to the advantage this fatty-acid/fluorescent label has in giving measurable fluorescence (GIMENO, paragraph 0083, 0149, 0082-0083).
ANCSIN and GIMENO teach of the claimed invention as shown above for Claim 1. They do not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having the structure of claim 2 with a substituted or unsubstituted phenyl group on the terminal methyl group of the fatty acid
GOODMAN is used to remedy this. GOODMAN teach using methyl-branched long-chain fatty acids such as 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (has a phenyl of terminal group of the pentadecanoic acid, fatty acid) are of interest as imaging/labeling agents (abstract). 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid has the “general,” formula as claimed in instant Claim 2.
Combining the fatty acid of GOODMAN with the labeling of ANCSIN and GIMENO, would give a fatty acid compound labeled with fluorescent substance having the “general,” formula as instantly claimed.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the fatty acid of GOODMAN as the fatty acid part of the fluorophore-fatty acid label in ANCSIN and GIMENO due to the advantage that this fatty acid has shown in having a pronounced uptake, which therefore gives better detection signal (GOODMAN, abstract).
With respect to Claim 5, ANCSIN teaches that this determination of triglyceride capacity is accomplished by using routine blood samples from patients and including assessing the endogenous lipoprotein lipase activity of blood leukocytes (white blood cells) to determine the specific deficiency causing the HTG (paragraph 0005).
This is done by (a) exposing a blood sample (which includes leukocytes) from the subject to a triglyceride substrate, wherein the triglyceride substrate undergoes a detectable change in fluorescence upon hydrolysis by LpL. The triglyceride substrate in this context just means triglyceride modified with a fluorophore to form a fluorogenic triglyceride substrate (e.g., a triglyceride analog having a terminal fluorophore on one or more fatty acid chains of the triglyceride) (paragraphs 0006-0007).
This blood sample containing the leukocytes with mixed with the fluorogenic substrate reads on the claimed, “first step of mixing,” and “thus bringing the fatty acid labeled with the fluorescent substance,” (triglyceride substate which has one or more fatty acids, labeled with fluorophore) “into contact with the leucocytes,” by mixing into a mixture (paragraph 0022-0023).
ANCSIN further teaches of acquiring a detectable increase in fluorescence/fluorescence intensity signal (value) upon hydrolysis from LpL (paragraph 0007, 0045, 0056), and thereby acquiring, “a value relating to the triglyceride metabolic capacity,” through broadest reasonable interpretation.
ANSCIN further teaches of acquiring either a single or multiple fluorescence measurements over multiple timepoints (paragraph 0056). ANSCIN shows that the difference of these measurements can be compared over time at that T0 is before binding and the other ones are after to see how they change (Figure 1 A & b, Figure 2, Figure 8, paragraph 0007-0008).
ANCSIN does not teach of the fatty acid of the triglyceride bound to the fluorophore specifically having the claimed structure, nor of removal of the fatty acid label compound from the sample after a period of time by washing.
GIMENO is used to remedy this. GIMENO further teaches of a method of using labeled fatty acids to detect compounds. This is analogous art to what the ANCSIN reference is doing by labeling the fatty acid component of triglycerides, to detect compounds in leucocytes.
Specifically, GIMENO teaches that a fatty acid labeled with BODIPY is used, and even more specifically that the compound which is used is BODIPY-fatty acid (4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid) (paragraph 0083, 0149). Of the fluorescent labeled fatty acid, 4,4-difluoro -5-methyl -4-bora -3a,4a-diaza-s-indacene-dodecanoic acid, the dodecanoic acid is the fatty acid. The formula for dodecanoic acid is C11H23COOH and it has 12 total carbons, 10 of which are in the fatty acid residue chain, so this reads on the instantly claimed 8 to 26 carbons and “a part of hydrogen atoms”. Dedecanoic acid also has a terminal methyl group, as another way to write it’s formula is CH3-(CH2)10-COOH. CH3 is the terminal methyl group. The claim limitation- “may,” “be substituted by an alkyl group having 1 to 3 carbon atoms,” is optional due to the, “may,” so this is not required by the claim.
GIMENO teaches of the structures for the labels as shown above and further teaches of removing the unincorporated fatty acid compound by washing and specifically that it is washing/removed after about 15-60 minutes, which falls in the claimed range (paragraph 0083, 0149).
The combination of ANSCIN And GIMENO make the claimed third through fifth steps obvious to one of ordinary skill in the art to perform.
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 fluorescent label/fatty acid pair as done in GIMENO having the claimed structure in the method of ANCSIN due to the advantage this fatty-acid/fluorescent label has in giving measurable fluorescence (GIMENO, paragraph 0083, 0149, 0082-0083). It would have further been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to remove or wash the extra unbound fatty acid fluorescent label after as certain amount of time as is done in GIMENO in the method of ANSCIN due to the advantage this has for stopping the uptake so that measurement can be performed (GIMENO, paragraph 0149).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
MOLINA in US 20180202993 teaches of ystems and methods of bioenergetic profiling, uses thereof, and systems and devices relating thereto. In particular, methods of the invention are useful in assessing wellness, particularly in elderly subjects. Described are systems and methods of assessing likelihood of subject morbidity, life expectancy, positive clinical outcome, responsiveness to treatment, and certain disease states as well as of selecting treatment strategy, improving outcome to treatment strategy, and treating subjects with low bioenergetic profiles. Also described are devices and systems for measuring respiratory capacity (abstract).
HUSSAIN in EP 1639125 teaches methods for assaying microsomal triglyceride transfer protein (MTP) which are amenable to automation and high-throughput screening. The assays may be used to measure MTP activity in cell and tissue homogenates as well as purified MTP. The methods provided by the present invention have the advantages of ease, rapidity, sensitivity, avoidance of the use of negatively charged lipids, versatility in studying different lipid transfer activities by purified and cellular MTP and the ability to measure inhibitory activity. In addition, methods of identifying compounds that modulate the lipid transfer activity of MTP are provided. Kits for measuring the lipid transfer activity of MTP are provided by the present invention (abstract). HUSSAIN further teaches of labeling lipids which can include triglycerides (which contain fatty acids) with BODIPY and other compounds (paragraph 00017-0021).
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 organizatio where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758