DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/7/25 is being considered by the examiner.
Claim Status
Claims 42-61 are pending and are examined. Claims 1-41 are cancelled.
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.
Claims 42-61 are rejected under 35 U.S.C. 103 as being obvious over Farokhzad (WO 2022/020272) in view of Macek (“Rapid determination of tamsulin in human plasma by high-performance liquid chromatography using extraction with butyl-acetate.” J Chromatography B. 809: 307-311 (2004)) and Maytash (“Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics” J. Lipid Research. 49:1137-1146).
The applied reference (WO 2022/020272) has a common applicant (i.e., Seer) and inventor (i.e., Daniel Hornburg) with the instant application.
Regarding Claim 42, Farokhzad teaches a method of assaying a biological sample, comprising:
providing the biological sample comprising a plurality of biomolecules, wherein the plurality of biomolecules comprises at least one lipid ([0097] A particle may comprise a lipid. A lipid-containing particle may comprise a lipid coupled to its surface (e.g., covalently attached to a surface amine of the particle or non-covalently bound by a particle-bound lipid binding protein), or may comprise a lipid within a monolayer or bilayer comprising the lipid. A lipid monolayer or bilayer may comprise non-lipidic biomolecules);
perform mass spectrometry ([0052] The collected biomolecule corona or the collected subset of biomolecules from the biomolecule corona may be analyzed (e.g., by mass spectrometry).
Farokhzad is silent to b. adding a first solvent to the biological sample to generate a mixture comprising a first organic layer and an aqueous layer, wherein the first organic layer comprises the at least one lipid, and wherein the first solvent comprises butyl acetate.
Macek teaches in the related art of assaying biomolecules. (See section 2.4. Preparation of the sample The samples were stored in the freezer at −18◦C and allowed to thaw at room temperature before processing. Ten microlitres of the internal standard solution (40ng) were added to 1ml of plasma, the tube was briefly shaken. One hundred microlitres of 1M sodium carbonate were added and the tube was shaken again. Then the mixture was vortex-mixed with 4ml of butyl acetate for 2min at 2000rpm. The tube was centrifuged 2min at 2000 × g and the upper organic phase was transferred to another tube. Tamsulosin was then back-extracted into 130 of 30mM potassium dihydrogenphosphate).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have included the steps of adding a first solvent to the biological sample to generate a mixture comprising a first organic layer and an aqueous layer, wherein the first organic layer comprises the at least one lipid, and wherein the first solvent comprises butyl acetate, as taught by Macek, to the method of modified Farokzhad, since butyl acetate has similar extraction characteristics and much lower solubility in water, as taught by Macek, in Section 1. Introduction, last sentence.
Modified Farokzhad is silent to c. performing mass spectrometry on the first organic layer, thereby identifying the at least one lipid.
Matyash teaches in the related art of lipid extraction. Recovered lipids were analyzed by TLC, and individual lipid species were quantified by shotgun DDA profiling on a quadrupole time-of-flight mass spectrometer. See page 1140, last paragraph of column 2.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of performing mass spectrometry on the first organic layer, thereby identifying the at least one lipid, as taught by Matyash, in the method, as taught by modified Farokzhad, to allow for accurate profiling of lipidomes, as taught by Matyash, in the Abstract.
Regarding Claim 43, modified Farokzhad teaches the method of claim 42, further comprising, contacting the biological sample, the first organic layer, or the aqueous layer with a surface, wherein the at least one protein binds to the surface ([0088] the compositions comprise various particle types, alone or in combination, which can be incubated with a wide range of biological samples to analyze the biomolecules (e.g., proteins) present in said biological sample based on binding to particle surface to form protein coronas.).
Regarding Claim 44, modified Farokzhad teaches the method of claim 42, further comprising performing mass spectrometry on the at least one protein ([0152] The collected biomolecule corona or the collected subset of biomolecules from the biomolecule corona may be analyzed (e.g., by mass spectrometry).
Regarding Claim 45, modified Farokhzad teaches the method of claim 42, wherein the first surface is a surface of particle ([0097] A particle may comprise a lipid. A lipid-containing particle may comprise a lipid coupled to its surface (e.g., covalently attached to a surface amine of the particle or non-covalently bound by a particle-bound lipid binding protein), or may comprise a lipid within a monolayer or bilayer comprising the lipid. A lipid monolayer or bilayer may comprise non-lipidic biomolecules).
Regarding Claim 46, modified Farokhzad teaches the method of claim 45, wherein the particle is a nanoparticle ([0101] a particle of the present disclosure may be a nanoparticle.).
Regarding Claim 47, modified Farokhzad teaches the method of claim 45, wherein the particle is a microparticle ([0102] In some cases, a particle of the present disclosure may be a microparticle.).
Regarding Claim 48, modified Farokhzad teaches the method of claim 42, wherein the first solvent does not comprise a halocarbon (Fig. 1. Methyl-tert-butyl ether (MTBE) lipid extraction method. Pg. 1140. TABLE 3. Recovery of lipids after extraction of plasma samples according to the MTBE. Pg. 1144.).
Regarding Claim 49, modified Farokhzad teaches the method of claim 42, further comprising adding a second solvent to the biological sample, the first organic layer or the aqueous layer (See TLC analysis. TLC analysis of lipid extracts was performed on Merck Silica Gel 60 HPTLC plates (10 3 10 cm). Plates were developed with an ethanol/CHCl3/triethylamine/water (40:35:35:9, v/v/v/v) solvent system, followed by n-hexane-ethylacetate (5:1, v/v). pg. 1138., 2nd column, 2nd paragraph from the bottom).
Regarding Claim 50, modified Farokhzad teaches the method of claim 49, wherein the second solvent comprises methyl tert-butyl ether (MTBE) (Fig. 1. Methyl-tert-butyl ether (MTBE) lipid extraction method. Pg. 1140. TABLE 3. Recovery of lipids after extraction of plasma samples according to the MTBE. Pg. 1144.).
Regarding Claim 51, modified Farokhzad teaches the method of claim 42, further comprising adding a pH adjusting agent to the biological sample, the first organic layer, the second organic layer, or the aqueous layer (See section 2.4 Preparation of the sample. Tamsulosin was then back-extracted into 130 μl of 30 mM potassium dihydrogenphosphate (pH of this buffer was adjusted to 2 with concentrated o-phosphoric acid) by shaking the tube for 2 min at 2000 rpm.).
Regarding Claim 52, modified Farokhzad teaches the method of claim 42, wherein the biological sample comprises plasma, serum, urine, cerebrospinal fluid, synovial fluid, tears, saliva, whole blood, milk, nipple aspirate, ductal lavage, vaginal fluid, nasal fluid, ear fluid, gastric fluid, pancreatic fluid, trabecular fluid, lung lavage, sweat, crevicular fluid, semen, prostatic fluid, sputum, fecal matter, bronchial lavage, fluid from swabbings, bronchial aspirants, fluidized solids, fine needle aspiration samples, tissue homogenates, lymphatic fluid, cell culture samples, or any combination thereof ([0089] The present disclosure provides several biological samples that can be assayed using the particles disclosed herein and the methods provided herein. For example, a biological sample may be a biofluid sample such as cerebral spinal fluid (CSF), synovial fluid (SF), urine, plasma, serum, tears, crevicular fluid, semen, whole blood, milk).
Regarding Claim 53, modified Farokhzad teaches the method of claim 52, wherein the biological sample comprises blood, serum, or plasma, or any portion of fraction thereof ([0089] The present disclosure provides several biological samples that can be assayed using the particles disclosed herein and the methods provided herein. For example, a biological sample may be a biofluid sample such as cerebral spinal fluid (CSF), synovial fluid (SF), urine, plasma, serum, tears, crevicular fluid, semen, whole blood, milk).
Regarding Claim 54, modified Farokhzad teaches the method of claim 42, further comprising purifying the at least one lipid from the first organic layer (See Lipid Profiling on pg. 1138, 1st column, last paragraph, All lipid samples were diluted in MS-mix buffer [7.5 mM ammonium acetate in chloroform-methanol-2-propanol (1:2:4, v/v/v)] and infused at the flow rate of 250 nl/min. A typical sample volume of 10 ml allowed 35 min of stable electro spray time.).
Regarding Claim 55, modified Farokhzad teaches the method of claim 42, wherein the at least one lipid comprises a phosphatidylcholine (PC), a phosphatidylglycerol (PG), cholesterol (Ch), a deuterated cholesterol, a diacylglycerol (DAG), a deuterated diacylglycerol, a phosphatidylserine (PS), a lysophosphatidylcholine (LPC), a ceramide (Cer), a phospatidylinositol (PI), a phosphatidic acid (PA), a phosphatidylethanolamine (PE), an acylcarnitine (AcCa), a lysophosphatidylethanolamine (LPE), a monoacylglycerol (MAG), a triacylglycerol (TAG), a dimethylammonium propane (DAP), a cholesteryl ester (ChE), a zymosterol (ZyE), a sterol ester (StE), a cardiolipin (CL), or a sphingomyelin (SM), or any derivative thereof ([0097] A particle may comprise a liposome. Examples of lipids that can be used to form the particles of the present disclosure include cationic, anionic, and neutrally charged lipids. For example, particles can be made of any one of or any combination of dioleoylphosphatidylglycerol (DOPG), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide).
Regarding Claim 56, modified Farokhzad teaches the method of claim 42, wherein the at least one lipid comprises a ChE, a CER, a CL, a DAG, a LPC, a LPE, a PG, a PE, a PI, a SM, or a TAG ([0097] A particle may comprise a liposome. Examples of lipids that can be used to form the particles of the present disclosure include cationic, anionic, and neutrally charged lipids. For example, particles can be made of any one of or any combination of dioleoylphosphatidylglycerol (DOPG), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide).
Regarding Claim 57, modified Farokhzad teaches the method of claim 42, wherein the performing mass spectrometry identifies at least about 1, 2, 3, 4, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000,or more distinct lipids (see Table 2 for lipids. 5 lipids are listed in Table 2).
Regarding Claim 58, modified Farokhzad teaches the method of claim 57, wherein the performing mass spectrometry comprises identifying cholesteryl esters (ChEs) in the biological sample (See Table 3, Column – cholesteryl ester. See pg. 1144).
Modified Farokhzad is silent to identifying at least about 10 cholesteryl esters (ChEs).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have identified at least about 10 cholesteryl esters (ChEs), in the method of modified Farokhzad, to allow for identifying a biological sample with more lipids.
Regarding Claim 59, modified Farokhzad teaches the method of claim 57, wherein the performing mass spectrometry comprises identifying ceramides (CERs) in the biological sample (Table 2. Ceramide).
Modified Farokhzad is silent to identifying at least about 10 ceramides.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have identified at least about 10 ceramides, in the method of modified Farokhzad, to allow for identifying a biological sample with more lipids.
Regarding Claim 60, The method of claim 57, wherein the performing mass spectrometry comprises identifying cardiolipins (CLs) in the biological sample.
Modified Farokkhzad is silent to identifying at least 10 cardiolipins (CLs).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have identified at least about 10 cardiolipins, in the method of modified Farokhzad, to allow for identifying a biological sample with more lipids.
Regarding Claim 61, modified Farokhzad teaches the method of claim 57, wherein the performing mass spectrometry comprises identifying diacyl glycerols (DAGs) in the biological sample (Table 2, diacylglycerol)
Modified Farokkhzad is silent to identifying at least 10 DAGs.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have identified at least about 10 diacyl glycerols (DAGs), in the method of modified Farokhzad, to allow for identifying a biological sample with more lipids.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
