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 the 18/579811 filed 08/26/2026.
Claims 32-38 are pending.
Claims 1-31 are cancelled.
This application has been examined as part of the PBA program.
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 non-obviousness.
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 32-38 are rejected under U.S.C. 103 as being obvious by WARNER in 'Prenatal Diagnosis of GM1 Gangliosidosis by Detection of Galactosyl-Oligosaccharides in Amniotic Fluid with High Performance Liquid Chromatography in view of JIANG in Oligosaccharide Biomarkers for Disease Progression and AAV Therapeutic Efficacy in Gangliosidosis and further in further view of DAGHER in 'Identification of Galectin-3 as a factor in pre-mRNA splicing' (all as cited on IDS dated 04/01/2024) and in further view of BOS in US 20120039843.
With respect to Claim 32, WARNER teaches of a method for detecting GM1-gangliosidosis in a subject having or suspected of having symptoms of GM1-gangliosidosis (page 1035, third paragraph) the method comprising:
'a' measuring pentasaccharide levels by HPLC (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph, and Table 1)
in a urine, a blood sample or a CSF sample obtained/provided by/from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph) and
'b' using the measurements of 'a' to classify the subject as having GM1- gangliosidosis (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph).
WARNER does not teach that the pentasaccharide detected is the claimed H3N2b.
WARNER does not teach the step of adding an internal standard, detecting the claimed H3N2b, or depleting one or more protein's or derivatizing one or more pentasaccharides.
JIANG is used to remedy this and teaches of detecting H3N2b for GM1-gangliosidosis, adding an internal standard (The H3N2b and its deuterated analog D 6 -H3N2b '6 hydrogen atoms in H3N2b are replaced by heavier stable isotope deuterium atoms' as internal standard are important to develop a fully validated FDA compliant assay for accurate and precise measurement of this biomarker in clinical samples; (first page, 1st and 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have detected GM1-gangliosidosis by H3N2b as is done in WARNER with the internal standard of JIANG, to provide the benefit of the utilizing an internal standard when measuring pentasaccharide levels in a urine sample and due to the importance and advantage deuterated standards offer for developing validated FDA assays for compliant accurate and precise measurement and since H3N2b was shown to be advantageous for measuring GM1-gangliosidosis (JIANG, first page, second paragraph).
WARNER and JIANG do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides.
DAGHER is used to remedy this and further teaches of depleting one or more protein's' (To test for a role of nuclear galectin-3 in pre-mRNA splicing, we used saccharide-affinity adsorption to deplete the protein from NEs;) (page 1215, first column, second paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention to have modified WARNER and JIANG with the depletion of one or more proteins as is done in DAGHER, due to the advantage this offers in providing the benefit of obtaining required proteins from a sample (page 1215, first column, second paragraph).
WARNER, JIANG, and DAGHER do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides or detection with mass spectrometry.
BOS is used to remedy this and teaches of derivatizing one or more pentasaccharides (The oligo- and pentasaccharide-spacer molecule may further be derivatized with linking residues such as the 'GMB' group, the N-hydroxy succinimide 'NHS' group or optionally protected thiol group to allow direct coupling with an optionally modified polypeptide (paragraph 0013). Further if it’s unclear that WARNER, JIANG, and DAGHER teach of the claimed detection of H3N2b in a pentasaccharide, BOS is also used to remedy this. Specifically, BOS teaches of 2NH.sub.3-3H].sup.3, which reads on the claimed detection of H3N2b in a pentasaccharide (paragraph 0094).
Specifically, BOS teaches of derivatization with an benzoic acid “or the like,” which reads on the claimed aminobenzoic acid (paragraph 0018).
BOS also teaches of detection by mass spectrometry (paragraph 0091) and also liquid chromatography measurement (paragraph 0056).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the derivatizing of BOS with the one or more pentasaccharides of BOS to detect the claimed 2NH.sub.3-3H].sup.3 or H3N2b due to the advantage this adds for changing the properties of the pentasaccharide which may be desired (BOS, paragraph 0013). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with detection through mass spectrometry as in BOS due to the advantage it has in measuring and comparing to isotopes to typical masses for identification of copmonents(paragraph 0091).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the amino benzoic acid of BOS due to the advantage such acids have in isolating salts or free bases (BOS, paragraph 0013).
With respect to Claim 33, WARNER and JIANG teach of the invention as shown above, but do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides.
DAGHER is used to remedy this and further teaches of depleting one or more protein's' (To test for a role of nuclear galectin-3 in pre-mRNA splicing, we used saccharide-affinity adsorption to deplete the protein from NEs;) (page 1215, first column, second paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention to have modified WARNER and JIANG with the depletion of one or more proteins as is done in DAGHER, due to the advantage this offers in providing the benefit of obtaining required proteins from a sample (page 1215, first column, second paragraph).
WARNER, JIANG, and DAGHER teach of the invention as shown above. They do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides with an amino benzoic acid.
BOS is used to remedy this and teaches of derivatizing one or more pentasaccharides (The oligo- and pentasaccharide-spacer molecule may further be derivatized with linking residues such as the 'GMB' group, the N-hydroxy succinimide 'NHS' group or optionally protected thiol group to allow direct coupling with an optionally modified polypeptide (paragraph 0013). Specifically, BOS teaches of derivatization with an benzoic acid “or the like,” which reads on the claimed aminobenzoic acid (paragraph 0018).
Further if it’s unclear that WARNER, JIANG, and DAGHER teach of the claimed detection of H3N2b in a pentasaccharide, BOS is also used to remedy this. Specifically, BOS teaches of 2NH.sub.3-3H].sup.3, which reads on the claimed detection of H3N2b in a pentasaccharide (paragraph 0094).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the derivatizing of BOS with the one or more pentasaccharides of BOS to detect the claimed 2NH.sub.3-3H].sup.3 or H3N2b due to the advantage this adds for changing the properties of the pentasaccharide which may be desired (BOS, paragraph 0013). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the amino benzoic acid of BOS due to the advantage such acids have in isolating salts or free bases (BOS, paragraph 0013).
With respect to Claim 34, WARNER teaches of a method for detecting GM1-gangliosidosis in a subject having or suspected of having symptoms of GM1-gangliosidosis (page 1035, third paragraph) the method comprising:
'a' measuring pentasaccharide levels by HPLC (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph, and Table 1)
in a urine, a blood sample or a CSF sample obtained/provided by/from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph) and
'b' using the measurements of 'a' to classify the subject as having GM1- gangliosidosis (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph).
WARNER does not teach that the pentasaccharide detected is the claimed H3N2b.
WARNER does not teach the step of adding an internal standard, detecting the claimed H3N2b, or depleting one or more protein's or derivatizing one or more pentasaccharides.
JIANG is used to remedy this and teaches of detecting H3N2b for GM1-gangliosidosis, adding an internal standard (The H3N2b and its deuterated analog D 6 -H3N2b '6 hydrogen atoms in H3N2b are replaced by heavier stable isotope deuterium atoms' as internal standard are important to develop a fully validated FDA compliant assay for accurate and precise measurement of this biomarker in clinical samples; (first page, 1st and 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have detected GM1-gangliosidosis by H3N2b as is done in WARNER with the internal standard of JIANG, to provide the benefit of the utilizing an internal standard when measuring pentasaccharide levels in a urine sample and due to the importance and advantage deuterated standards offer for developing validated FDA assays for compliant accurate and precise measurement and since H3N2b was shown to be advantageous for measuring GM1-gangliosidosis (JIANG, first page, second paragraph).
WARNER and JIANG do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides.
DAGHER is used to remedy this and further teaches of depleting one or more protein's' (To test for a role of nuclear galectin-3 in pre-mRNA splicing, we used saccharide-affinity adsorption to deplete the protein from NEs;) (page 1215, first column, second paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention to have modified WARNER and JIANG with the depletion of one or more proteins as is done in DAGHER, due to the advantage this offers in providing the benefit of obtaining required proteins from a sample (page 1215, first column, second paragraph).
WARNER, JIANG, and DAGHER do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides or detection with mass spectrometry.
BOS is used to remedy this and teaches of derivatizing one or more pentasaccharides (The oligo- and pentasaccharide-spacer molecule may further be derivatized with linking residues such as the 'GMB' group, the N-hydroxy succinimide 'NHS' group or optionally protected thiol group to allow direct coupling with an optionally modified polypeptide (paragraph 0013). Further if it’s unclear that WARNER, JIANG, and DAGHER teach of the claimed detection of H3N2b in a pentasaccharide, BOS is also used to remedy this. Specifically, BOS teaches of 2NH.sub.3-3H].sup.3, which reads on the claimed detection of H3N2b in a pentasaccharide (paragraph 0094).
Specifically, BOS teaches of derivatization with an benzoic acid “or the like,” which reads on the claimed aminobenzoic acid (paragraph 0018).
BOS also teaches of detection by mass spectrometry (paragraph 0091) and also liquid chromatography measurement (paragraph 0056).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the derivatizing of BOS with the one or more pentasaccharides of BOS to detect the claimed 2NH.sub.3-3H].sup.3 or H3N2b due to the advantage this adds for changing the properties of the pentasaccharide which may be desired (BOS, paragraph 0013). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with detection through mass spectrometry as in BOS due to the advantage it has in measuring and comparing to isotopes to typical masses for identification of copmonents(paragraph 0091).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the amino benzoic acid of BOS due to the advantage such acids have in isolating salts or free bases (BOS, paragraph 0013).
With respect to Claim 35, WARNER teaches of a method for detecting GM1-gangliosidosis in a subject having or suspected of having symptoms of GM1-gangliosidosis (page 1035, third paragraph) the method comprising:
'a' measuring pentasaccharide levels by HPLC (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph, and Table 1)
in a urine, a blood sample or a CSF sample obtained/provided by/from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph) and
'b' using the measurements of 'a' to classify the subject as having GM1- gangliosidosis (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph).
WARNER does not teach that the pentasaccharide detected is the claimed H3N2b.
WARNER does not teach the step of adding an internal standard, detecting the claimed H3N2b, or depleting one or more protein's or derivatizing one or more pentasaccharides.
JIANG is used to remedy this and teaches of detecting H3N2b for GM1-gangliosidosis, adding an internal standard (The H3N2b and its deuterated analog D 6 -H3N2b '6 hydrogen atoms in H3N2b are replaced by heavier stable isotope deuterium atoms' as internal standard are important to develop a fully validated FDA compliant assay for accurate and precise measurement of this biomarker in clinical samples; (first page, 1st and 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have detected GM1-gangliosidosis by H3N2b as is done in WARNER with the internal standard of JIANG, to provide the benefit of the utilizing an internal standard when measuring pentasaccharide levels in a urine sample and due to the importance and advantage deuterated standards offer for developing validated FDA assays for compliant accurate and precise measurement and since H3N2b was shown to be advantageous for measuring GM1-gangliosidosis (JIANG, first page, second paragraph).
With respect to Claim 36, WARNER teaches of detection in a urine, a blood sample or a CSF sample obtained/provided by/from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph)
With respect to Claim 37, WARNER teaches of a method for detecting GM1-gangliosidosis in a subject having or suspected of having symptoms of GM1-gangliosidosis (page 1035, third paragraph) the method comprising:
'a' measuring pentasaccharide levels by HPLC (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph, and Table 1)
in a urine, a blood sample or a CSF sample obtained/provided by/from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph) and
'b' using the measurements of 'a' to classify the subject as having GM1- gangliosidosis (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph).
WARNER does not teach that the pentasaccharide detected is the claimed H3N2b.
WARNER does not teach the step of adding an internal standard, detecting the claimed H3N2b, or depleting one or more protein's or derivatizing one or more pentasaccharides.
JIANG is used to remedy this and teaches of detecting H3N2b for GM1-gangliosidosis, adding an internal standard (The H3N2b and its deuterated analog D 6 -H3N2b '6 hydrogen atoms in H3N2b are replaced by heavier stable isotope deuterium atoms' as internal standard are important to develop a fully validated FDA compliant assay for accurate and precise measurement of this biomarker in clinical samples; (first page, 1st and 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have detected GM1-gangliosidosis by H3N2b as is done in WARNER with the internal standard of JIANG, to provide the benefit of the utilizing an internal standard when measuring pentasaccharide levels in a urine sample and due to the importance and advantage deuterated standards offer for developing validated FDA assays for compliant accurate and precise measurement and since H3N2b was shown to be advantageous for measuring GM1-gangliosidosis (JIANG, first page, second paragraph).
WARNER and JIANG do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides.
DAGHER is used to remedy this and further teaches of depleting one or more protein's' (To test for a role of nuclear galectin-3 in pre-mRNA splicing, we used saccharide-affinity adsorption to deplete the protein from NEs;) (page 1215, first column, second paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention to have modified WARNER and JIANG with the depletion of one or more proteins as is done in DAGHER, due to the advantage this offers in providing the benefit of obtaining required proteins from a sample (page 1215, first column, second paragraph).
WARNER, JIANG, and DAGHER do not teach of depleting one or more protein's or derivatizing one or more pentasaccharides or detection with mass spectrometry.
BOS is used to remedy this and teaches of derivatizing one or more pentasaccharides (The oligo- and pentasaccharide-spacer molecule may further be derivatized with linking residues such as the 'GMB' group, the N-hydroxy succinimide 'NHS' group or optionally protected thiol group to allow direct coupling with an optionally modified polypeptide (paragraph 0013). Further if it’s unclear that WARNER, JIANG, and DAGHER teach of the claimed detection of H3N2b in a pentasaccharide, BOS is also used to remedy this. Specifically, BOS teaches of 2NH.sub.3-3H].sup.3, which reads on the claimed detection of H3N2b in a pentasaccharide (paragraph 0094).
Specifically, BOS teaches of derivatization with an benzoic acid “or the like,” which reads on the claimed aminobenzoic acid (paragraph 0018).
BOS also teaches of detection by mass spectrometry (paragraph 0091) and also liquid chromatography measurement (paragraph 0056).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the derivatizing of BOS with the one or more pentasaccharides of BOS to detect the claimed 2NH.sub.3-3H].sup.3 or H3N2b due to the advantage this adds for changing the properties of the pentasaccharide which may be desired (BOS, paragraph 0013). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with detection through mass spectrometry as in BOS due to the advantage it has in measuring and comparing to isotopes to typical masses for identification of copmonents(paragraph 0091).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified WARNER, JIANG, and DAGHER with the amino benzoic acid of BOS due to the advantage such acids have in isolating salts or free bases (BOS, paragraph 0013).
With respect to Claim 38, WARNER teaches of a method for detecting GM1-gangliosidosis severity in a subject (The HPLC technique provides a sensitive, facile, ancillary method to enzyme assay for screening and diagnosis, and it allows delineation between the infantile-, juvenile and adult-onset subtypes.; page 1034, second paragraph) having or suspected of having symptoms of GM1-gangliosidosis (In the study a male with the clinical picture of infantile GM1 gangliosidosis, presented at about age 6 months with failure to thrive, coarse facial features, hepato-splenomegaly, corneal clouding, and bony changes on radiological examination that were consistent with GM, gangliosidosis; page 1035, third paragraph) the method comprising: 'a' measuring pentasaccharide levels (the OS pattern obtained with neonatal urine from a GM, gangliosidosis patient showed the two linear pentasaccharides and the biantennary octasaccharide being the most abundant components; page 1040, third paragraph) in a urine, a blood sample or a CSF sample obtained from the subject (urine was obtained from patients who were diagnosed as being affected with infantile GM, gangliosidosis based on their clinical phenotype and beta-galactosidase deficiency; page 1035, fourth paragraph) and 'b' using the measurements of 'a' to classify the severity GM1- gangliosidosis (The HPLC technique provides a sensitive, facile, ancillary method to enzyme assay for screening and diagnosis, and it allows delineation between the infantile-, juvenile and adult-onset subtypes.; page 1034, second paragraph).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 2019/213612 A1 (as cited on IDS dated 04/01/2024)(WASHINGTON UNIVERSITY) (Hereinafter "WASH') discloses a method for treating a subject or monitoring the effectiveness of a therapeutic agent (a method for treating a subject as described; page 38, [0087]) the method comprising 'a' providing a first biological sample obtained from a subject (a method for treating a subject as described above may comprise 'a' providing an isolated tau sample obtained from a subject and measuring, in the isolated tau sample, tau phosphorylation at one or more amino acid residues; page 38, [0087]) 'b' administering a pharmaceutical composition to the subject ('b' administering a pharmaceutical composition to the subject when the measured phosphorylation levels' significantly deviate; page 38, [0087]) 'c' providing a second biological sample obtained from the subject sometime after administration of the pharmaceutical composition (in another embodiment, a method for treating a subject as described above may comprise 'a' providing a first and a second isolated tau sample obtained from a subject and measuring; page 38, [0087]). WASH does not disclose 'd' measuring in each sample a pentasaccharide level.
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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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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