DETAILED ACTION
Preliminary Amendment filed on 12/08/2022 is acknowledged. Claims 1-27 are pending in the application and are considered on merits.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 4-7, 9-11, 13, 17-22 and 24-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pan et al. (BMC Ophthalmology, 2020, IDS) (Pan).
Regarding claim 1, Pan teaches a diagnosing method for the risk of an ocular disease development or for the disease progression of an end-stage ocular disease by molecular profile analysis of the ocular anterior tissue microenvironment (abstract), comprising a step of
measuring the concentration level of a metabolite appearing in the collected aqueous humor specimens by mass spectrometry (MS) (page 2, par 2, 4, 5).
Regarding claim 2, Pan teaches that wherein the ocular disease is glaucoma (page 2, par 2).
Regarding claim 4, Pan teaches wherein the mass spectrometry (MS) is gas chromatography-mass spectrometry (GC-MS) (page 2, par 4) and/or liquid chromatography-mass spectrometry (LC-MS).
Regarding claim 5, Pan teaches that wherein the metabolite is contained in extracellular vesicle (EVs) in the aqueous humors (inherently). Extracellular vesicles (EVs) present in the aqueous humor, that inherently contain a variety of metabolites.
Regarding claim 6, Pan teaches that the diagnosing method further comprising a step of selecting a metabolite that shows different molecular dynamics from that in tear fluid or blood (The VIP values exceeding 1 were first selected as changed metabolites) (page 3, par 0).
Regarding claim 7, Pan teaches that wherein glaucoma is primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), or pseudoexfoliative glaucoma/pseudoexfoliative syndrome (PEG) (page 7, par 1).
Regarding claim 9, Pan teaches wherein the metabolite is selected from those common or not common with the bias observed in subjects with corneal endothelial failures. Metabolites are either common or not common with the bias observed in subjects with corneal endothelial failures.
Regarding claim 10, Pan teaches that wherein the metabolite is at least one selected from the group consisting of sugar or polyol, a product in the citric acid cycle, acylcarnitine, polyamine, amino acid, and cAMP (Table 1).
Regarding claim 11, Pan teaches that wherein the sugar or polyol is arabinonic acid, myo-inositol, or fructose; the product in the citric acid cycle is citric acid or isocitric acid; the acylcarnitine is carnitine, isobutyrylcarnitine (C4), or propionylcarnitine; the polyamine is spermidine; and the amino acid is asy-dimethylarginine, quinolinic acid, cysteine, or 3-methylhistidine (Table 1).
Regarding claim 13, Pan teaches that wherein the metabolite is at least one selected from the group consisting of 2- aminoadipic acid, mannose, GSH (glutathione), alanine, spermine, asparagine, choline, glutamine, glutamic acid, pyroglutamic acid, acetylcholine, xanthosine, N-acetylarginine, glycine, 3-aminoisobutyric acid, cystine, kynurenine, kynurenic acid, 4-hydroxyproline, pyridoxic acid, isocitric acid, N-acetylglucosamine, GSSG (glutathione disulfide), N'-formyl kynurenine, creatinine, N-acetylmethionine, omithine, citrulline, oleamide, arabitol, adenosylhomocysteine, hippuric acid, trans-urocanic acid, urea, succinic acid, riboflavin, 2-hydroxyglutaric acid, malic acid, hypotaurine, pipecolinic acid, guanidinoacetic acid, acetylcamosine, 2-oxoglutaric acid, 3-hydroxyisovaleric acid, maltose, uridine, 1,5-anhydro-Dsorbitol, fucose, and 2-aminoethanol (Table 1).
Regarding claim 17, Pan teaches that the diagnosing method comprising a step of referring to the result of comprehensive proteome analysis in the molecular profiles of proteinaceous molecules contained in extracellular vesicle (EVs) in the aqueous humors (page 3, par 2).
Regarding claim 18, Pan teaches that the diagnosing method comprising a step of referring to findings in proteome analysis and/or gene expression analysis using clinical specimens (page 2, par 1).
Regarding claim 19, Pan teaches that the diagnosing method comprising a step of referring to information pertaining to factors in tear fluid, blood, and/or other body fluids (page 6, par 1).
Regarding claim 20, Pan teaches a diagnosing marker for evaluating the risk of ocular disease development or for diagnosing the disease progression of end-stage ocular diseases, which is used in the diagnosing method according to Claim 1 (Table 1).
Regarding claim 21, Pan teaches that the diagnosing marker is at least one selected from the group consisting of sugar or polyol, a product in the citric acid cycle, acylcamitine, polyamine, amino acid, and cAMP (Table 1).
Regarding claim 22, Pan teaches that wherein the sugar or polyol is arabinonic acid, myo-inositol, or fructose; the product in the citric acid cycle is citric acid or isocitric acid; the acylcamitine is camitine, isobutyrylcamitine (C4), or propionylcamitine; the polyamine is spermidine; and the amino acid is asy-dimethylarginine, quinolinic acid, cysteine, or 3-methylhistidine (Table 1).
Regarding claim 24, Pan teaches that at least one diagnosing marker is selected from the group consisting of 2-aminoadipic acid, mannose, arabinonic acid, myoinositol, cAMP, fructose, asy-dimethylarginine, citric acid, quinolinic acid, cysteine, spermidine, carnitine, isobutyrylcarnitine (C4), 3-methylhistidine, propionylcarnitine, GSH (glutathione), alanine, spermine, asparagine, choline, glutamine, glutamic acid, pyroglutamic acid, acetylcholine, xanthosine, N-acetylarginine, glycine, 3-aminoisobutyric acid, cystine, kynurenine, kynurenic acid, 4-hydroxyproline, pyridoxic acid, isocitric acid, Nacetylglucosamine, GSSG (glutathione disulfide), N'-formylkynurenine, creatinine, Nacetylmethionine, ornithine, citrulline, oleamide, arabitol, adenosylhomocysteine, hippuric acid, trans-urocanic acid, urea, succinic acid, riboflavin, 2-hydroxyglutaric acid, malic acid, hypotaurine, pipecolinic acid, guanidinoacetic acid, acetylcarnosine, 2-oxoglutaric acid, 3-hydroxyisovaleric acid, maltose, uridine, 1,5-anhydro-D-sorbitol, fucose, and 2-aminoethanol (Table 1).
Regarding claim 25, Pan teaches a diagnosing system for the risk of an ocular disease development or for the disease progression of an end-stage ocular disease (abstract) comprising a means for collecting aqueous humor specimens and a means for analyzing the specimens by mass spectrometry (MS), which is used in the diagnosing method according Claim 1 (page 2, par 2, 4, 5).
Regarding claim 26, Pan teaches that wherein the ocular disease is glaucoma (page 2, par 2).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 3, 8, 14-16 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pan et al. (BMC Ophthalmology, 2020, IDS) (Pan).
Regarding claim 3, in conclusion, Pan teaches that “As a result, 14 metabolites were identified as potential biomarkers that could discriminate between patients with POAG and controls” (page 7, par 1). Thus, Pan fairly suggests that the collected aqueous humor specimens from a subject in a pre-disease stage with no clinically abnormal signs of ocular disease without identification of the pathological characteristics of the ocular disease can be used for diagnosing ocular disease stage with no clinically abnormal signs of ocular disease.
Regarding claim 8, Pan teaches that “We identified fourteen metabolites as possible biomarkers in aqueous humor samples that had the potentials to distinguish POAG patients from controls” (page 6, par 0).
It would have been obvious to one of ordinary skill in the art to apply Pan’s method to identify more metabolites as possible biomarkers in aqueous humor samples that has the potentials distinguish normal tension glaucoma (NTG), and pseudoexfoliative glaucoma/pseudoexfoliative syndrome (PEG) patients from controls, by routine experimentation.
Regarding claim 14-15, Pan does not specifically teach that wherein the glaucoma is normal tension glaucoma (NTG), or pseudoexfoliative glaucoma/pseudoexfoliative syndrome (PEG). However, Pan teaches that “We identified fourteen metabolites as possible biomarkers in aqueous humor samples that had the potentials to distinguish POAG patients from controls” (page 6, par 0). Pan teaches mannose and spermidine as possible markers (Table 1).
It would have been obvious to one of ordinary skill in the art to apply Pan’s method to identify more metabolites as possible biomarkers in aqueous humor samples that has the potentials distinguish normal tension glaucoma (NTG), and pseudoexfoliative glaucoma/pseudoexfoliative syndrome (PEG) patients from controls, by routine experimentation.
Regarding claim 16, as has been discussed regarding claim 14-15 above, it would have been obvious to one of ordinary skill in the art to apply Pan’s method to identify more metabolites as possible biomarkers in aqueous humor samples that has the potentials to discriminate among the occurrence of retinal ganglion cell degeneration or the preceding susceptibility of retinal ganglion cells to degeneration stress or cell death, or the vulnerability of retinal ganglion cells, by routine experimentation.
Regarding claim 27, as has been discussed regarding claim 14-15 above, it would have been obvious to one of ordinary skill in the art to apply Pan’s method to identify more metabolites as possible biomarkers in aqueous humor samples that has the potentials to diagnose corneal endothelial failures, by routine experimentation.
Allowable Subject Matter
Claim 12 and 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The prior art of record does not teach or fairly suggest that wherein the sugar or polyol is arabinonic acid or myo-inositol; the acylcarnitine is isobutyrylcarnitine (C4); and the amino acid is cysteine.
Conclusion
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797