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 17/259264 RCE filed 10/17/2025.
Claims 1-6, 9-10, & 21-22 are pending and have been fully examined.
Claims 14-15 are withdrawn from consideration.
Claims 7-8, 11-13, & 16-20 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 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 1-2, 5, 9-10 & 21-22 are rejected under 35 U.S.C. 103 as being obvious over SAARINEN in US 20040253651 in view of LEE in Comprehensive N-Glycome profiling of cultured human epithelial breast cells identifies unique secretome N- glycosylation signatures enabling tumorigenic subtype classification and further in view of UEDA in US 8653448.
With respect to Claims 1 & 9, SAARINEN teaches of a method for diagnosing cancer in a biological sample by determining the presence of a LAcdiNAc oligosaccharide sequence/LAcdinNAc structure (abstract, paragraph 0050-0055). SAARINEN further teaches that the cancer can be prostate cancer (paragraph 0016), and that cancer can be detected from a glycoprotein and one of the preferred cancer associated proteins that is used for detection and is analyzed is prostate specific antigen (PSA) (paragraph 0054, 0016) that is a cancer specific antigen that includes cancer specific oligosaccharides(this makes the method a test method, “for” prostate cancer, as broadly claimed- though prostate cancer is only claimed in the claim preamble).
SAARINEN et al. also teach of detecting modifications in the sugar/glycan chains (paragraph 0142, 0153). SARRINEN et al. further teaches of cancer specific LacdiNAc type containing GalNAcB1-4GlcNAc-oligosaccharide sequences that can be detected and characterized by antibodies, lectins, and even further of using mass spectrometry for detection (paragraph 0055-0058).
SAARINEN et al. also teach of monitoring sialylation (paragraphs 0023-0030, 0032, 0041, 0060, 0099, 0101, 0146, 0155, 0165) (this would include monitoring of any multi-sialylated compounds if present, since “sialylated glycans,” are monitoring, though the word multi-sialylated is not used).
SAARINEN et al. teach of detecting relative abundances of components (paragraph Table 1, 0041, 0141)- this reads on measuring relative abundances of at least one or more of Glycan ID: 7512, Glycan ID: 7603, Glycan 3401, and/or Glycan ID 5602,” and also of the sialylated structures---however measuring for abundances does not require that the compounds are actually found to be present. SAARINEN teaches of any presence of LacdiNac structure indicating cancer (this reads on assessing a grade of cancer- any amount of cancer is a grade of cancer) and which reads on “abundance above a predetermined value,” (abstract).
SAARINEN et al. teach of monitoring oxonium to analyze the sugar chains. SAARINEN teach that LC-ESI MS (mass spectrometry) can be used to monitor the oxonium ions of SA and of Hex and of Hex-HexNAc (paragraph 0021).
Though SAARINEN teaches of detection of sialylated compounds as shown above which would include multi-sialylated structures, since multi-sialylated structures are not specifically mentioned (which seem to be part of Glycan ID 7512 & 7603), LEE is used to remedy this.
LEE et al. teach of a method for detecting N-glycosylation signatures in cancer(abstract). LEE et al. more specifically teach that the N-glycan modifications taught therein play a key role in the development and progression of cancers including prostate cancer (Page 4784, column 1, paragraph 2). LEE et al. further teach they detected significant levels of highly sialyated and fucosylated type N-glycans (abstract, Page 4784, column 1, paragraph 2, Figures 1-2), and specifically teach of analyzing cancer cells with three of more terminal sialic acid residues (this is a multi-sialylated compound) (Page 4790, column 1, paragraph 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 multi-sialyated structure level as is done in LEE in the method of SAARINEN to detect cancer and specifically prostate cancer due to the need in the art for comprehensive and accurate profiling of proteins for all types of cancer (LEE, Page 4784, column 1, paragraph 2).
SAARINEN and LEE doe not teach of the claimed mass spectrometry method which is specifically mass spectrometry with energy resolved oxonium monitoring or Erexim, which is the tradename for this method.
UEDA is used to remedy this and more specifically teaches of method that is capable of determining a glycan structure with high detection sensitivity, a method of the present invention includes the steps of: carrying out triple quadrupole mass spectrometry at various values of CID energy; creating an energy-resolved profile including yield curves representing relationships between (i) a value of the CID energy and (ii) measured amounts of specific types of product ions; preparing a reference profile, and identifying a glycan structure of a test material by comparing the energy-resolved profile with the reference profile (abstract). Even more specifically, UEDA teaches of using energy-resolved oxonium monitoring to create and energy resolved oxonium profile for identification of glycan structures (Column 12, example 1, last paragraph- Col 13, first paragraph).
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 energy resolved oxonium monitoring as is done in UEDA in to detect the multisialyated structures in LacdiNac in glycans for prostate cancer diagnosis as is done in SAARINEN and LEE due to the advantage energy resolved oxonium monitoring has in that it makes it possible to determine a glycan structure with high detection sensitivity (UEDA, Column 4, lines 5-8).
With respect to Claim 2, SAARINEN et al. teach of detecting relative abundances of components (paragraph 0041, 0141). LEE et al. also teach of detecting relative abundance of each glycan (Page 4785, column 2, paragraph 3, Page 4788, column 2, last paragraph).
Further with respect to Claim 2, in the instant specification- Page 11, paragraph 1, it is noted that the Glycan ID defines the type of glycan, and the digits correspond to the numbers of HexNAc, Hexose, Fucose, and Neu5Ac from the left, respectively. Figure 2 A, paragraph 0054, and Figure 4 A & B show further scans and structures for Glycan ID’s 7512 & 7603. However, as claimed, “analyzing,” does not involve any isolating or synthesizing. Therefore- since the prior art references shown above teach of detecting relative abundances- teaches of the instantly claimed “analyzing,” even if they do not call attention to these species.
With respect to Claims 5 & 10, SAARINEN et al. teach of analyzing in a serum samples (paragraph 0067, Claim 7).
With respect to Claims 21-22, SAARINEN et al. teach of using serum as the sample (paragraph 0032).
Claims 3-4 & 6 are rejected under 35 U.S.C. 103 as being obvious over SAARINEN in US 20040253651 in view of LEE in Comprehensive N-Glycome profiling of cultured human epithelial breast cells indentifies unique secretome N- glycosylation signatures enabling tumorigenic subtype classification and further in view of ZHANG in US 20160069884.
With respect to Claim 3, SAARINEN and LEE teach of the instant invention as shown in the above rejection. See above the rejection for Claim 2. They do not teach of using logistic regression for analysis. ZHANG et al. is used to remedy this.
ZHANG et al. teach of methods for distinguishing between varying levels of prostate cancer(abstract). ZHANG et al. further teach of detecting fucosylated prostate specific antigen (PSA)(abstract), and further of detecting N-glycans (paragraph 0163, 0183). ZHANG et al. further teach of using logistic regression to mathematically analyze the biomarker panels (paragraph 0101, 0115). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use logistic regression to analyze biomarkers as is done in ZHANG in the methods of SAARINEN and LEE due to the advantage it has in ability of correlated the biomarkers with the disease (paragraph 0101).
With respect to Claim 4, SAARINEN And LEE teach of the claimed invention as shown in the above 103 rejection. SAARINEN and LEE et al. do not teach of the instantly claimed formula using logistic regression and Gleason analysis to predict prostate cancer. ZHANG et al. is used to remedy this. ZHANG et al. teaches of both Gleason calculation analysis for prostate cancer (paragraphs 0026-0030, 0160-0161), and the use of logistic regression (which uses the natural logarithm as instantly claimed in the formula) and many other mathematical and statistical analyses (paragraph 0101). Though- ZHANG et al. does not teach of inputting the claimed values that applicant does instantly- the instant formula as claimed is not tied to the instant purpose- at least clearly so, and what is claimed is performing a general calculation/plugging in numbers to an equation. It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use logistic regression to analyze biomarkers as is done in ZHANG in the methods of SAARINEN and LEE due to the advantage it has in ability of correlated the biomarkers with the disease (paragraph 0101). Further, it would have been obvious to one of ordinary skill in the art to plug numbers into and equation and perform general math.
With respect to Claim 6, SARRINEN and LEE et al. teach of the claimed invention as shown in the above rejection, however they do not teach of the patient having PSA at a level in the range of 4 ng/ml to 10ng/ml. ZHANG et al. teach of patients having a PSA level that falls within this range (1.9 to 26.6 ng/ml). This includes the range claimed, so therefore the instantly claimed range is taught by ZHANG.
Response to Arguments
Applicant's arguments filed 10/17/2025 have been fully considered but they are not persuasive.
With respect to the prior 101, the instant amendments dated 10/17/2025 make the claims overcome the prior 101 rejection. This is because, “mass spectrometry with an energy-resolved oxonium ion monitoring method,” makes the claims as a whole amount to significantly more than the claimed natural correlation judicial exceptions at step 2B of the 101 analysis. Mass spectrometry with an energy-resolved oxonium ion monitoring method, is not well-understood, routine and conventional in the art and is closer to a “needle in a haystack.” Applicant’s arguments and the prior Declaration submitted by Dr. Koji Ueda were helpful to this affect as well.
With respect to the 103 rejection and the prior art, applicant argues that no one piece of prior art teaches of the whole claimed method.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The examiner maintains that the 103 rejection shown above, with a newly added reference UEDA, which shows the energy resolved oxonium monitoring, makes the instant invention obvious.
Applicant argues that the SAARINEN reference does not teach of the claimed energy resolved oxonium monitoring, but of only monitoring of oxonium. The examiner points out a new reference, UEDA teaches of the energy resolve oxonium monitoring, as shown above. Therefore, the instant invention is made obvious.
Applicant does not make any substantive arguments about the LEE of ZHANG references.
All claims remain rejected.
Conclusion
Though not limited to this- or relied upon in the instant rejections, other relevant prior art was found upon examination:
FUKUSHIMA in α1,2-Fucosylated and β-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer.
In applicant’s instant specification they describe structure of Glycan ID: 7512 is shown in Fig. 3A/4A:
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And structure of Glycan ID: 7603 is shown in Fig 3B/4B.
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These are multisialyated LacdiNAc structures, as applicant gives a key for the subunits-though there is not indicator in the specification of what the white open box shape unit is:
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FUKUSHIMA et al. teach of a method of detecting biomarkers for PSA in serum(abstract). FUKUSHIMA, teaches in Figure 2, of structures which read on these structures with Glycan ID 7512 and 7603 as disclosed by applicant (see Figure 2 of FUKUSHIMA directly below:
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The structures taught above are both “sugar chain modifying PSA,” and multisialylated and analyzed for LacdiNAc structure (see Page 455, first column,
Page 458, column 1, paragraph 1 first column).
TABERES in Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA.
TABERES et al. teach of a monitoring PSA glycan structures in prostate cancer patients. TABERES seems to identify the presence of GalNAc as significant (abstract, and full article). For the instant claims, what sets the claimed HexNAc7 glycans apart from other PSA glycans is the presence of a GalNAc residue, where other glycans have only (up to 6) GlcNAcs (the instant 7512 and 7603 IDS must have 7).
YABU in Occurrence of free deaminoneuraminic acid (KDN)-containing complex-type N-glycans in human prostate cancers.
YABU et al. teach of a method of analyzing neuraminic acid containing complex type N-glycans in human prostate cancers(abstract). YABU et al. further teach of analyzing modified sugar chains (Page 635, column 1, second paragraph & column 2, last paragraph) in the sample, of monitoring carbohydrate antigens as tumor markers (Page 634, column 2, last two lines), and also of analyzing LacdiNac structure (Page 6535, column 2, last paragraph).
LI in Detection and Verification of Glycosylation Patterns of Glycoproteins from Clinical Specimens Using Lectin Microarrays and Lectin-Based Immunosorbent Assays. 2011
LI et al. teach of method for observing glucosylation differences in PSA in prostate cancer patients(abstract). LI finds that in metastatic prostate cancer there is 1) increased Neu5Acα2-6 sialylated glycans as evidenced byincreased binding on SNA and PSL; (2) galactosylated glycansthat were detected by the increased binding to Jacalin and PTAgal; (3) manosylated, glucosylated, or N-acetylglucosaminylatedglycans detected by increased binding to lectin LcH B; and (4)increased N-acetylgalactosaminylated glycans that were detectedwith WFA (Figure 2A and Supplementary Table 1 in the Sup-porting Information)(Page 8512, column 1, paragraph 1).
KAMMEIJER in An In-depth glycosylation assay for urinary prostate-specific antigen. 2018(cited on IDS dated 09/03/2021).
KAMMEIJER et al. teach of measuring PSA in serum to detect prostate cancer(abstract). KAMMEIJER et al. further teach of detecting PSA glycosylation (such as atenna modification and focosylation). KAMMEIJER et al. further teach of monitoring the 10 most common glycopeptides in PSA (Figure 1,2, 3).
US 8653448 by UEDA
UEDA et al. teach of an analysis method that determines glycan structure(abstract). Figure 2 shows the determined glycan structures.
US 20110294141 by YAMASHITA
YAMASHITA et al. teach of a method for distinguishing prostate cancer and analyzing PSA (abstract). YAMASHITA et al. teach of the method including affinity for .beta.-N-acetylgalactosamine residues and/or a lectin having an affinity for fucose .alpha.(1, 2) galactose residues with a sample possibly containing PSA(abstract).
HIRANO in US 20110236995
HIRANO is used to remedy this and further teaches of a method of detecting glycan structure of prostate specific antigen which has a LacdiNAc structure (abstract) and also of detecting sialic acid structures (paragraph 0006, 0089, 0097). HIRANO teaches of using blot analysis (paragraph 0081, 0112, 0147), and electrophoresis (paragraph 0087,0110-0111). HIRANO teach of specifically using WFA lectin as a binding molecule for the LacdiNAc glycans (paragraph 0103, 0102). It would have been obvious to one of ordinary skill in the art to use WFA, in analysis for detection of glycans as is done in HIRANO in the methods of SAARINEN and LEE due to its advantages of being able to recognize a non-reduced GaINAc terminal when detection LacdiNAc (HIRANO, paragraph 0103).
Conclusion
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