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 16/575909 appeal brief filed 06/16/2026.
Claims 1, 3-4,7, & 29-44 have been examined and fully considered.
In view of the appeal brief filed on 06/16/2026, PROSECUTION IS HEREBY REOPENED. A Non-Final rejection is set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
Claims 1, 3-4,7, & 29-44 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: Independent Claims 1, 37, & 41 are directed towards methods.
Step 2A, Prong One: Independent Claims 1, 37 and 41 recite abstract ideas which are the “identifying,” and “quantifying,” claim limitations in the claim preambles and claim bodies. These are mental processes, which are abstract idea judicial exceptions. “Comparing,” based on the claimed identifying is also a mental process, which again is an abstract idea judicial exception.
Claim 41 contains the additional limitation in the preamble of “diagnostic screening,” in addition to the other judicial exceptions already mentioned above. “Screening,” as claimed is mental process which is an abstract idea. The “diagnostic,” part is based on an amount of lipids in the sample and its correlation with a “medical condition.” This correlation is an abstract ideas itself (mathematical correlation,) and the diagnostic part is a las of nature judicial exception.
See MPEP 2106.04 (a) and & 2106.04(b).
Step 2A, Prong Two: The abstract idea or natural correlation in independent Claims 1, 37 & 41 are not integrated into a practical application because upon or after the comparison and “identifying,” nothing further is done to practically apply.
Also- the claimed obtaining of a library (data) and measurement of “discrete bands of lipids,” by an LC and MS measuring/measurement steps using multiple reaction monitoring (MRM) as instantly claimed is just data gathering to perform the judicial exceptions. Use of and combination of a sample with stable isotope labeled lipids standards is also used for data gathering/comparison as claimed.
Data gathering is considered to be insignificant extra-solution activity and does not practically apply the judicial exception. See MPEP 2106.05 (g).
Step 2B: There is nothing in independent Claims 1, 37 & 41 which add something which is non routine and conventional or significantly more to the claimed abstract idea or natural correlation judicial exceptions.
Obtaining of a library (data) and measurement of “discrete bands of lipids,” by an LC and MS measuring/measurement steps using multiple reaction monitoring (MRM) as instantly claimed are all well understood, routine and conventional (WURC) in the art and therefore there is nothing significantly more as claimed.
“This is evidenced by HERMANN in US 20190300920 in view of Lipids Maps Mass Spectrometry Chapters (from here on out referred to as LIPIDS) and further in view of CHRISTIE in Rapid Separation and Quantification of lipid classes by high performance liquid chromatography and mass light scattering detection.
HERMANN teaches of quantifying lipids (by mass spectrometry) ,
in a mixture comprising classes of lipids and wherein the classes of lipids can include phosphatidylethanolamines(one class of lipids), phosphatidylglycerols(a second class of lipid), and phosphatidylinositols (a third class of lipids) (Table 7).
HERMANN further teaches that the stable isotope lipid standards are used for lipid extraction and added to the sample (paragraph 0223-0224), and that after the sample is extracted it is then enriched with the stable isotopes/ “stable isotope labeled standards,” (which reads on the instantly claimed combining known concentrations of SILs with the sample to form a sample matrix), and then mass spectrometry is performed in multiple reaction mode (MRM) on the whole matrix to obtain MRM transitions (paragraph 0245, 0246, 0252-0265). HERMANN also teaches that liquid chromatography is used for separation (paragraph 0242-0243, 0247).
LIPIDS teaches of measuring the lipids and introducing the sample matrix into an LC then to MS/MS(Page 101, 8.) to separate the lipids into bands—the separate bands are shown in the figures—the peaks can be otherwise referred to as bands (Page 363 & 366 Figure 14.8, 14.7).
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein. “cholesteryl esters and triacylglycerols were clearly resolved, diacylglycerols formed a shoulder on the cholesterol peak and that unesterified fatty acids were eluted just ahead of the phospholipids. Phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), and ceramide eluted together, but phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine were eluted as sharp peaks followed by sphingomyelin(SPH) (two bands), with the bands, being the lines of the formed peaks—and showing discrete bands for separate lipid classes (See Figure 1 on page 509 and also shown below & Page 509, left column, Figure 1 description, starting with bolded “Fig. 1,” through end of column).
Further, see MPEP 2106.05(d)- “laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner.”
The dependent claims 3-4, 7 & 29-36, 38-40, & 42-44 are analyzed the same way as above.
Claims 3-4 specify that MRM transitions are monitored in negative and positive mode and what biomolecule they are from. This does nothing to practically apply at step 2A,2 and is also WURC at step 2B, so not significantly more.
Claim 7 specifies that proteins are precipitated. However, this does nothing to practically apply at step 2A,2 and is also WURC at step 2B so not significantly more.
Claims 29-32, 34-36, 39, 40 43-44, specify what the lipid mixture is that is separated out and what isotope standards are used. However, this does nothing to practically apply and the detection is data gathering as shown for the independent claims at step 2A,2 and LC and MS (using MRM) and isotope standards (SIL) and deuterated standards are WURC at step 2B so not significantly more.
Claim 33, 38, 42 specifies that the sample is plasma. However, this does nothing to practically apply as is the sample the detection is data gathered from as shown for the independent claims at step 2A,2 and using plasma is WURC so not significantly more at step 2B.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 3-4, 7 & 29-44 are rejected under 35 U.S.C. 103 as being obvious over HERMANN in US 20190300920 in view of Lipids Maps Mass Spectrometry Chapters (from here on out referred to as LIPIDS) and further in view of CHRISTIE in Rapid Separation and Quantification of lipid classes by high performance liquid chromatography and mass light scattering detection.
With respect to Claim 1, 37, & 41 HERMANN teaches of a method for production of and use of stable isotope labeled lipids and their use as internal standards for mass spectrometry methods (abstract).
HERMANN more specifically teaches the method involves identifying and quantifying lipids (by mass spectrometry) as instantly claimed,
in a mixture comprising classes of lipids and wherein the classes of lipids can include phosphatidylethanolamines(one class of lipids), phosphatidylglycerols(a second class of lipid), and phosphatidylinositols (a third class of lipids) (Table 7), and wherein the identifying can include identifying/diagnosing various medical diseases including diabetes obesity and aging (paragraph 0114).
HERMANN further teaches that the stable isotope lipid standards are made from lipid extraction of processed yeast cells (paragraph 0223-0224), and that after the sample is extracted it is then enriched with the stable isotopes/ “stable isotope labeled standards,” (which reads on the instantly claimed combining known concentrations of SILs with the sample to form a sample matrix), and then mass spectrometry is performed in multiple reaction mode (MRM) on the whole matrix—though the term matrix is not used a combination of sample and SILs as claimed in the sample matrix and this is what is taught by HERMANN-to obtain MRM transitions (paragraph 0245, 0246, 0252-0265). HERMANN also teaches that liquid chromatography is used for separation (paragraph 0242-0243, 0247).
Even further, HERMANN teaches of separation by electrophoresis ( which would also separate into discrete bands)(paragraph 0089).
HERMANN even further teaches of that the stable isotope labeled lipids can comprise five or more stable isotope labelled lipids (the SIL as instantly claimed)(paragraph 0109), and that these stable isotope lipids can be combined with the sample and used as internal standards (paragraph 0001, abstract). Further, HERMANN teaches that this stable isotopic labeled (lipid) can be used as an internal standard which is added to the sample to be analyzed at the beginning of sample preparation, in defined known concentrations (paragraph 0002). So—in the case that the lipid stable isotopic lipid standards contain five or more stable isotope lipids--- 5 defined known concentrations of the lipids are added (paragraph 0002).
The signals of both the stable isotope lipid standards (5 of them) and the corresponding analyte/s in the sample are simultaneously detected and they are correlated to a calibration curve established with the same concentration of the internal standards (which have the 5 lipid stable isotopic standards) and different known concentrations of the corresponding analyte. Through these steps, the lipids/analyte in the sample are identified and quantified (paragraph 0002, 0246).
Though HERMANN makes it obvious, they do not specifically teach of measuring the lipids by themselves by MRM, nor of obtaining”/ providing a “library,” for MRM transitions within the classes of lipids in the mixture and they do not call out separation of into discrete bands as claimed.
LIPIDS et al. is used to remedy this. LIPIDS teaches of methods for detecting lipids through mass spectrometry (Title page, and Table of contents). LIPIDS et al. further teach of synthesizing and using 18 deuterium labeled internal standards (Page labeled 2, first paragraph & Introduction on Page 2 & Page 3, 2.2) to detect triglycerols/ides, and further of measuring a biological sample that has multiple classes of lipids in it including phosphatidylcholines, phosphatidylinosiltols (Page 31, paragraph 3, line 9) and even further of analysis of sphingolipids (Page 28, last paragraph & Figure 4.6)(Page 351, abstract, line 3).
LIPIDS teaches of measuring the lipids and introducing the sample matrix into an LC then to MS/MS(Page 101, 8.) to separate the lipids into bands—the separate bands are shown in the figures—the peaks can be otherwise referred to as bands (Page 363 & 366 Figure 14.8, 14.7).
LIPIDS et al. further teach of comparing of the measured samples to a calibration curve generated from the internal standards (Page 5, 3.1.3 & 3.1.4). LIPIDS et al. further teach that the lipid extracts are analyzed to find changes from normal sources to show the status of a biological condition such as a disease (Page 25, paragraph 1).
Even further, LIPIDS teaches of measuring the lipids using MRM mode (Page 63, 2.5, line 3) and even further that a library of MRM transitions is obtained and used (Page 74, 3.1 MRM transition selection, line 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to measure or compare to a library of MRM transitions and other conditions to detect a class or classes of lipids as is done in LIPIDS in the method of HERMANN due to the advantage this offers for calculating the presence or concentration of unknown lipids (Page labeled as 11, 4.2, paragraph 1) and further to make the internal standard as chemically and structurally similar to the target analyte as possible(Page 64, last paragraph) and it would have been obvious to compare to LC and MS conditions libraries due to the advantage this offers for knowing the recoveries the systems are know to achieve which offers further advantage in gauging detection accuracy (Page 79, 3.4, paragraph 1, line 3-4). It further would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to separate into discrete classes for comparison of lipids to standards as is done in LIPIDS due to the advantage this has in aiding in detection accuracy by showing a high equivalence between ion yields of the naturally occurring analytes with the selected standards (Page 102, first paragraph).
HERMANN and LIPIDS do not use the word band to described the separation, so and if separation into discrete bands as claimed is unclear CHRISTIE is used to remedy this.
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein. “cholesteryl esters and triacylglycerols were clearly resolved, diacylglycerols formed a shoulder on the cholesterol peak and that unesterified fattyacids were eluted just ahead of the phospholipids. Phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), and ceramide eluted together, but phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine were eluted as sharp peaks followed by sphingomyelin(SPH) (two bands), with the bands, being the lines of the formed peaks—and showing discrete bands for separate lipid classes (See Figure 1 on page 509 and also shown below & Page 509, left column, Figure 1 description, starting with bolded “Fig. 1,” through end of column).
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to separate the lipids into bands by lipids by HPLC as is done in CHRISTIE in the methods of HERMANN and LIPIDS due to the advantage this method has in having good separation of lipids and stable recorder baseline in spike of abrupt changes of solvent composition during various times in the analysis (Page 509, left column, Figure 1 description, starting with bolded “Fig. 1,” through end of column Also see Figure 1).
With respect to Claim 3, HERMANN al. teach of MRM detection in both positive and negative ion mode (paragraph 0246, 0248). LIPIDS teaches of monitoring in positive and negative ion mode (Page 104, Page 354, lines 14-15 & Page 31, second paragraph).
With respect to Claim 4 & 18, HERMANN teaches of the claims as shown above for Claim 1, but does not teach of the MRM transitions claimed. LIPIDS et al. teach of normalization of neutral loss data for the different groups of fatty acyl groups. It would have been obvious to detect such groups do to the advantage this has for sample identification (Page labeled as 11, 4.2, paragraph 1). See reason for combination from Claim 1.
With respect to Claim 7, HERMANN teaches of the claims as shown above for Claim 1, but does not teach of removing proteins by protein precipitation. LIPIDS et al. teach of using HPLC for extraction and of using isopropanol for the extraction/purification/precipitation of the lipids and removal of other components by centrifugation (Page 102, 8.1, 1., Page 3, 2.3 & Page 33, 5.4, Page 152, 5., paragraph 2), of using a vortex and centrifuge which would cool the sample and take place for 5 plus minutes or so and cooling with nitrogen (Page 5, 3.1.4). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to precipitate protein and unwanted un lipid components as is done in LIPIDS in the method of HERMANN due to the advantage this offers for precipitation of precipitate in reconstituted samples (Page 102, 8.1, 1.).
With respect to Claim 29, HERMANN teaches that the mixture can comprise LPC, PC, and SM(sphingomyselin) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). HERMANN does not teach specifically separation of LPC, PC and SM.
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein LPC is separated from PC and SM (which is SPH on Figure 1 of christie). See reason for combination from Claim 1.
With respect to Claim 30, HERMANN teaches that the mixture can comprise ceramides, hexosylceramides and sphingolipids (which include sphingomyelins) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). LIPIDS teaches of separation of SMs and Ceramindes and Hex ceramides (Figure 14.7). HERMANN does not teach specifically separation of TG, HexCer, SMs, and Cer
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein TG, HexCer, SMs(Which is SPH on figure 1 of christie), and Cer (Page 509, Fig 1, Christie). See reason for combination from Claim 1.
With respect to Claim 31, HERMANN teaches that the mixture can comprise LPC, PC, and SM (sphingomyelin) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). HERMANN teaches that the mixture can comprise ceramides, hexosylceramides and sphingolipids (which include sphingomyelins) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). HERMANN further teaches of using radyl phospholipids (Page 25, last paragraph).
HERMANN does not teach of all of the claimed classes including MG, DG, TG, cholesterol, cholesterol ester, PG, PE, LPE, and PIs or Pas.
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein TG, MG, DG, cholesterol, cholesterol esters, PG, PE, LPE and PI are all taught on figure 1 of christie)See reason for combination from Claim 1.
With respect to Claim 32, HERMANN teaches that the mixture can comprise LPC, PC, and SM (sphingomyelin) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). HERMANN teaches that the mixture can comprise ceramides, hexosylceramides and sphingolipids (which include sphingomyelins) and that the SIL standards are deuterated versions of these (paragraph 0099), (paragraph 0067). HERMANN further teaches of using radyl phospholipids (Page 25, last paragraph). HERMANN does not teach of all of the claimed classes including MG, DG, TG, cholesterol, cholesterol ester, PG, PE, LPE, and PIs or Pas.
CHRISTIE teaches of a method for separation of lipid classes by HPLC(abstract). CHRISTIE further teaches of separation of lipids/lipid classes by HPLC, wherein TG, MG, DG, cholesterol, cholesterol esters, PG, PE, LPE and PI are all taught on figure 1 of christie)See reason for combination from Claim 1.
With respect to Claim 33, HERMANN and LIPIDS teach of the above, but do not call out plasma sample CHRISTIE is used to remedy this and teaches specifically of detection of plasma lipids (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 plasma as is done in CHRISTIE due to the heavy makeup in the plasmas of different lipids and due to the advantage this would offer for a sample in a method of analyzing lipids (Page 509, column 2, 3 paragraphs from bottom).
With respect to Claim 34, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with MS conditions. LIPIDS teaches that the library also includes MS conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
With respect to Claim 35, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with MS conditions. LIPIDS teaches that the library also includes MS conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
With respect to Claim 36, HERMANN teaches of the SIL including deuterated lipid standards (paragraph 0067). LIPIDS also teaches of using 18 different deuterium labeled internal standards (Page 2, first paragraph).
With respect to Claim 38, HERMANN and LIPIDS teach of the above, but do not call out plasma sample CHRISTIE is used to remedy this and teaches specifically of detection of plasma lipids (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 plasma as is done in CHRISTIE due to the heavy makeup in the plasmas of different lipids and due to the advantage this would offer for a sample in a method of analyzing lipids (Page 509, column 2, 3 paragraphs from bottom).
With respect to Claim 39, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with LC conditions. LIPIDS teaches that the library also includes LC conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
With respect to Claim 40, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with MS conditions. LIPIDS teaches that the library also includes MS conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
With respect to Claim 42, HERMANN and LIPIDS teach of the above, but do not call out plasma sample CHRISTIE is used to remedy this and teaches specifically of detection of plasma lipids (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 plasma as is done in CHRISTIE due to the heavy makeup in the plasmas of different lipids and due to the advantage this would offer for a sample in a method of analyzing lipids (Page 509, column 2, 3 paragraphs from bottom).
With respect to Claim 43, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with LC conditions. LIPIDS teaches that the library also includes LC conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
With respect to Claim 44, HERMANN teaches of the claims as shown above , but does not teach of the library claimed with MS conditions. LIPIDS teaches that the library also includes MS conditions for obtaining the transitions (See Table 3.1 with retention times and limit of detection and recovery). See reason for combination from Claim 1.
Response to Arguments
The examiner notes that the instant application was re-opened to add a 101 rejection to the record. This was done after consultation with the examiner’s SPE and the TC 101 consultants.
Applicant's arguments filed in appeal brief dated 06/16/2026 have been fully considered but they are not persuasive. Applicant’s arguments appear on pages 13-23 of appeal brief dated 06/16/2026.
The examiner notes that the instant application was re-opened to add a 101 rejection to the record. This was done after consultation with the examiner’s SPE and the TC 101 consultants. The 103 rejection was also updated, adding a new reference, the CHRISTIE references as shown in the above rejection. The Hansen and McKenna references are no longer used.
All claims remain rejected.
With respect to the prior art, applicant argues that independent claims 1, 37, & 41 have the feature of "introducing the sample matrix into a liquid chromatography (LC) system to separate lipids in the sample matrix into discrete bands of lipids, wherein each discrete band of lipids comprises lipids of the same class, and wherein each class of lipids appears in a single band,” in common, and that the combination of prior art does not teach of this. The examiner disagrees that the prior art does not teach of this and again notes the new prior art used, and how the term “band,” can be interpreted.
Notably, LIPIDS reference does teach of detection of discrete --- and specifically teaches of measuring the lipids and introducing the sample matrix into an LC to separate the lipids into bands—the separate bands are shown in the figures (Page 101, Page 363 & 366 Figure 14.8, 14.7). However, since LIPIDS just does not call them “bands,” as the bands formed are not seen with the human eye in techniques like liquid chromatography and instead are registered by a machine and turned into peaks on a graph and visually show the separated bands by liquid chromatography (like on the Figures 14.8 and 14.7, in LIPIDS). Therefore, LIPIDS is considered to teach this part.
If this is still not clear though—the new reference CHRISTIE is used to teach of this as shown in the prior art rejection above. CHRISTIE specifically uses both peaks and bands to describe the claimed HPLC chromatogram (Page 509, Figure 1, left column, starting at the bolded “Fig. 1.)
Applicant further argues that there are advantages of separating lipids into bands of lipids prior to analysis and that specifically the advantage is that the number of lipids having the same molecular weight makes identification and quantification difficult, so that only performing mass spectrometry on discrete bands of lipids allows for more rapid analysis, wherein only classes of lipids need to be separated versus separating individual lipids.
With respect to this, the examiner notes that they can see why there is advantage to this and thanks applicant for the description of this.
Applicant further goes into detail with respect to what the separate classes of lipids claims can be and the possibilities disclosed for these classes and recites with respect to Example 2 of applicant’s instant specification. With respect to Example 2 of applicant’s instant specification, applicant argues that it shows to be linear of 4 orders of magnitude and has sufficient sensitivity to allow for the analysis at systemic levels in human plasma. Applicant argues that the prior art does not teach or show of these advantages.
Again, with respect to this, the examiner thanks applicant for drawing attention to this and the examiner agrees that the prior art does not seem to recite these particular advantages, however, applicant does not claim anything about more rapid analysis or sensitivity or orders of magnitude. Therefore, though the examiner does not doubt that the instant invention has advantage, it is not recited in the claims if so.
Applicant further argues that they think the prior art does not teach of separation into bands by LC prior to mass spectrometry. Applicant also argues that the examiner does not appear to consider that each discrete band contains lipids of the same class. The examiner disagrees with this, and the LIPIDS reference does in fact teach of this, though they do not teach of the word “bands,” they still teach of this with how broadly the term bands can be interpreted.
Specifically, LIPIDS teaches of measuring the lipids and introducing the sample matrix into an LC then to MS/MS(Page 101, 8.) to separate the lipids into bands— wherein the bands are lipids of separate(with the same “class,” lipids showing in each band) classes, the separate bands are shown in the figures—the peaks can be otherwise referred to as bands (Page 363 & 366 Figure 14.8, 14.7).
Applicant argues that each peak ( or band) in Figure 14.7 of LIPIDs shows individual lipids, and not “bands based on class.” The examiner disagrees. As long as the individual different lipids in LIPIDS are from different lipid classes, they can be considered separated into discrete bands based on lipid class, as instantly claimed. This is the case in LIPIDS as Ceramides, and Sphingomyelins are shown, which are different classes of lipids (Lipids, page 363, Figure 14.7 description).
Applicant compares Figure 14.7 and 14.8 of LIPIDS to Applicant’s example 2 found in their instant specification and specifies that in their example all different types of ceramides are grouped together, all different HexCeramides are grouped together as so on. With respect to this, the examiner notes that applicant has not claimed this specifically, so that this comparison to instant application Example 2, is not commensurate in scope with the instant claims.
Applicant argues with respect to the Hansen and McKenna references, however these references are no longer used, so this is not commensurate in scope with the instant rejection.
With respect to Claim 29, applicant argues that the prior art does not teach of separation into 3 distinct classes of lipids as claimed (PCs, SMs, and LCs.). The examiner disagrees. The examiner notes that the newly used Christie teaches of this. Please see the rejection above.
With respect to Claim 30, applicant argues that the prior art does not teach of separation into the distinct classes of lipids as claimed (TG, HexCer, SMs, and Cer). The examiner disagrees. The examiner notes that the newly used Christie helps teach of this. Please see the rejection above.
With respect to Claim 31, applicant argues that the prior art does not teach of separation into the distinct 8 classes of lipids as claimed (MG, DG, TG, cholesterol, cholesterol ester, PG, PC, PE, SM, LPC, LPE, and PIs or Pas) The examiner disagrees. The examiner notes that the newly used Christie helps teach of this. Please see the rejection above.
With respect to Claim 32, applicant argues that the prior art does not teach of separation into the distinct 8 classes of lipids as claimed ( PG, PE, LPE, and PIs) The examiner disagrees. The examiner notes that the newly used Christie helps teach of this. Please see the rejection above.
With respect to Claims 29-32, applicant also argues about McKenna, however this reference is no longer used, so this is not commensurate in scope with the instant rejection.
All claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
LACOLLA in US 20090305258
LACOLLA teaches of method for separating and quantifying lipids out from a samples (paragraph 0068, 0072). LACOLLA further teaches of separating lipid subclasses by bands using thin layer chromatography and the bands of separate lipids were identified by comparison with standards which are run simultaneously (paragraph 0083).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to separate lipids into discrete bands as is done in LACOLLA in the methods of HERMANN, LIPIDS, and MCKENNA due to the advantage this offers for identification when in comparison with standards (LACOLLA, paragraph 0083).
MCKENNA in US 20120328594
MCKENNA teaches of a method for detecting lipid and/or protein biomarkers (abstract). MCKENNA further teaches of the sample being in a sample matrix (paragraph 0244), of separating by electrophoresis which would separate discrete bands (paragraph 0283, 0211), and of assaying for lipids by spiking the samples with an internal standard (which has three odd chain analogs of the lipids CE 15:1, CE 170:0, and LY 17:0)), then precipitating the proteins by adding MeOH/CHC13 and then centrifuging the samples and then of analyzing the analyte (lipids) by mass spec and HPLC and by comparison to a calibration curve (paragraph 0324).
MCKENNA further teaches of the separation (paragraph 0276) wherein binding indicates the discrete classes of lipids/detection and wherein detection can also be by thin-layer chromatography (which separates into discrete bands (paragraph 0211). MCKENNA further teaches that the peak area ratios of analyte/internal standard) are calculated and converted to absolute analytes concentrations using the calibration curves (paragraph 0324). This reads on the claimed quantifying the separated lipid classes (CE 15:1, CE 17:0, LY 17:0) based on a comparison between the detector response and known concentrations of the standards (paragraph 0324).
HANSEN in US 10705100
HANSEN teaches of methods for accurately comparing the levels of ionizable lipids in two cell populations that differ in some respect from each other using mass spectroscopy and isotopic labeling are provided. The methods can be used to identify a change in a lipid of interest in response to a cellular, chemical, genetic, or environmental change to the cell population (i.e., a lipid response to a cell perturbation). The change in the lipid of interest can be a change in composition, rate of synthesis, and/or location of the lipid (abstract).
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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