DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1, 4, 21, 22, 25, 26 and 37-39 are pending.
Claim 39 has been added.
Claims 1, 25, 26, 37 and 38 have been amended.
Claims 1, 4, 21, 22, 25, 26 and 37-39 are examined on the merits.
3. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Objections
Claim Objections
4. Claim 26 is no longer objected to because it properly depends from a pending claim, see Amendments to the Claims submitted April 29, 2026.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
5. The rejection of claim 26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of the amendment to the claim, see Amendments to the Claims submitted April 29, 2026, page 2.
6. Claim 26 recites the limitation with sufficient antecedent basis for limitations in the claim, see Amendments to the Claims submitted April 29, 2026, page 2.
7. The rejection of claim 25 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of the amendment to the claim, see Amendments to the Claims submitted April 29, 2026, page 2.
Claim Rejections - 35 USC § 102
8. The rejection of claim(s) 1, 4, 25, 26 and 38 under 35 U.S.C. 102(a)(1) as being anticipated by Skog et al., US 2010/0196426 A1 (published August 5, 2010), as evidenced by Kagan et al. (Journal of Clinical Ligand Assay 25 (1): 104-110, Spring 2002) is withdrawn in light of Applicant’s arguments presented in the Remarks submitted April 29, 2026, page 5.
9. The rejection of claim(s) 37 under 35 U.S.C. 102(a)(1) as being anticipated by Okada et al., US 2009/0253147 A1 (published October 8, 2009) is withdrawn in light of Applicant’s amendment to the claim and corresponding arguments, see Amendments to the Claims, page 3 and Remarks, page 6, both submitted April 29, 2026.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
10. 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.
11. 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.
12. The rejection of claim(s) 1, 4, 21, 22, 25, 26, 37, 38 and new claim 39 under 35 U.S.C. 103 as being unpatentable over Skog et al., US 2010/0196426 A1 (published August 5, 2010), as evidenced by Kagan et al. (Journal of Clinical Ligand Assay 25 (1): 104-110, Spring 2002), and further in view of Huang et al., US 2011/0256155 A1 (published October 20, 2011) and Pawlowski et al., WO 2012/170711 A1 (published 13 December 2012) is maintained and made.
Applicant argues “[t]here is no rationale for why CDON and SVA2 expression would be measured in the same sample on the basis of Skog.”, see page 6 of the Remarks submitted April 29, 2026, 5th paragraph (para.).
Applicant follows with the teachings of Kagan, Huang and Pawlowski, stating “[t]hese references cannot repair the [alleged] deficiency…” of Skog, see last full para. on page 6 of the Remarks.
Applicant concludes arguments noting the references fail to remedy the alleged defects and the combination of references cannot render the claimed invention obvious, see para. bridging pages 6 and 7.
These arguments have been carefully considered, but fail to persuade.
Skog teaches “…methods of aiding diagnosis, prognosis, monitoring and evaluation of a disease or medical condition…by detecting a biomarker…”, wherein the disease may be pancreatic cancer and the biological sample includes blood utilizing a number of isolation methods and techniques, see Abstract; page 2; page 6; and entire document. The tables therein cite numerous biomarkers that inform one of skill in the art if detected it/they should be regarded as an identifying biomarker for disease. As established in the instant rejection, Skog teaches SV2A, CDON, IL6ST, ARSA, TIMP2, SULF2 and CD55, see herein.
The secondary references provide further teachings of implementing isolation techniques and desired biological sample(s) and their components, nucleic acids and/or polypeptides.
Hence, the combination of the references continues to teach the claimed invention and all the claim limitations, see rejection herein. The modification of the primary reference in light of the secondary references is proper because the applied references are so related that the appearance of features shown in one would suggest the application of those features to the other. See In re Rosen, 673 F.2d 388, 213 USPQ 347 (CCPA 1982); In re Carter, 673 F.2d 1378, 213 USPQ 625 (CCPA 1982), and In re Glavas, 230 F.2d 447, 109 USPQ 50 (CCPA 1956). Further, it is noted that case law has held that a designer skilled in the art is charged with knowledge of the related art; therefore, the combination of old elements, herein, would have been well within the level of ordinary skill. See In re Antle, 444 F.2d 1168,170 USPQ 285 (CCPA 1971) and In re Nalbandian, 661 F.2d 1214, 211 USPQ 782 (CCPA 1981). The combination of references would not change the principle of operation of the prior art invention being modified, hence the teachings of the references are sufficient to render the claims obvious. For the reasons of record and cited herein, the rejection is maintained.
Skog teaches assaying surface antigens, molecules and biomarkers on microvesicles isolated from a blood sample, see sections 0010 and 0011; and page 6, sections 0119 and 0122. “[M]icrovesicles are secreted by tumor cells and circulating in bodily fluids.”, see section 0114. The biomarker associated with a disease is nucleic, see section 0014. Skog teaches size exclusion chromatography, see claims 10, 14, 26, 30, 41, 45, 60 and 64 spanning pages 106-108. Size exclusion chromatography (SEC) is art known to be a technique and a specific type of hydrodynamic size-based separation.
It is art known that blood from cancer patients have the increased propensity to contain tumor cells including circulating tumor cells (CTCs) and regarded by the Examiner as classical circulating tumor cells. As evidenced by Kagan, “CTC[s] can be detected in the blood of patients with carcinomas, albeit at extremely low frequencies.”, see page 108, 1st sentence in Discussion.
The blood samples are obtained from individuals with pancreatic cancer are assayed, see page 2, sections 0012-0016 and 0020.
The assayed biomarkers are synaptic vesicle glycoprotein 2A (SV2A) on page 79, 2nd column; interleukin 6 cytokine family signal transducer (IL6ST) with FC 0.61 on page 49 and page 91, 2nd column; cell differentiation 55 (CD55) with FC 4.11 on page 43; arylsulfatase A (ARSA) with FC 0.70 on page 48 and page 71, 2nd column; tissue inhibitor of metallopeptidase 2 (TIMP2) on page 56, 1st column; sulfatase 2 (SULF2) on page 79, 2nd column and page 88, 1st column; and cell adhesion associated oncogene regulated (CDON) on page 82, 1st column.
Skog does not teach the gene expression product measured is a polypeptide and the level of integrin subunit alpha 6 (ITGA6) is measured. Skog also does not teach a level of expression products of no more than 100 or 200 other genes is determined.
However, Huang teaches the first step of collecting blood from an individual and enriching the sample for CTCs by the use of ferrofluid coated antibodies targeting designated antigens, see page 4, section 0045. The blood sample is collected from an individual with a tumor or cancer including pancreatic cancer, see page 3, sections 0024-0026 and 0029. Huang also teaches no more than 100 or 200 other genes are assayed, see entire document.
Moreover, Pawlowski teaches assessing circulating structures for surface proteins and/or biomarkers within blood for analysis of cancers including pancreatic cancer, see abstract; page 2, section 0010; page 4, section 0021; page 4, section 0017; page 5, section 0024; page 11, section 0054; page 14, section 0064; page 44, section 00188; page 45, section 00194; page 63, section 00271; and page 166, section 00610. Vesical associated biomarkers include ITGA6, see pages 82 and 85, last 5 lines, as well as TIMP2 on page 75, line 4 and section 00317, page 79, 1st row, page 80, 2nd row, page 84, 3rd row; and CD55 on page 82.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to isolate CTCs from the blood sample utilizing hydrodynamic size-based separation via SEC and assay for multiple gene expression products including ITGA6 and in the manner taught by all references, herein.
One of ordinary skill in the art would have been motivated to combine the isolation and separation techniques of Skog and Huang to enrich and differentiate the CTCs from all other cells in the blood sample to measure and accurately profile the gene expression products of interest with a reasonable expectation of success exemplified in the said prior art documents, see all documents in their entirety.
Moreover, one of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success exemplified in all prior art documents, wherein numerous gene products that are polypeptides have been isolated, identified and measured within blood successfully, see all documents in their entirety.
13. The rejection of claim(s) 37 under 35 U.S.C. 103 as being unpatentable over Skog et al., US 2010/0196426 A1 (published August 5, 2010), and further in view of Pawlowski et al., WO 2012/170711 A1 (published 13 December 2012) is maintained.
Applicant recites the limitations of claim 1, which differ from those of claim 37, see Remarks submitted April 29, 2026, page 7, 3rd paragraph (para.).
Applicant attempts to diminish Skog’s disclosure of CDON and SV2A stating it “…is no more than inclusion in lists, ‘Genes containing somatic mutations in breast cancer’” and “Genes containing somatic mutations in pancreatic cancer.”, respectively, see Remarks, page 7, 3rd para.
Applicant argues “[t]here is no rationale for why CDON and SVA2 expression would be measured in the same sample on the basis of Skog.”, see page 7 of the Remarks, 3rd para. There is no argument as to the teaching of SULF2.
Applicant concludes arguments stating Pawlowski “…[teaches] no more than assessing biomarkers in blood of cancer patients.” And the combination of references fail to “…render the claimed invention obvious.”, see page 7, paragraphs (paras.) 4-6.
These arguments have been carefully considered, but fail to persuade.
Skog teaches “…methods of aiding diagnosis, prognosis, monitoring and evaluation of a disease or medical condition…by detecting a biomarker…”, wherein the disease may be pancreatic cancer and the biological sample includes blood utilizing a number of isolation methods and techniques, see Abstract; page 2; page 6; and entire document. The tables therein cite numerous biomarkers that inform one of skill in the art if detected it/they should be regarded as an identifying biomarker for disease. As established in the instant rejection, Skog teaches SV2A, CDON and SULF2, see herein.
The secondary reference provides further teachings of to arrive and desired biological sample(s) and their components, nucleic acids and/or polypeptides.
Hence, the combination of the references continues to teach the claimed invention and all the claim limitations, see rejection herein. The modification of the primary reference in light of the secondary references is proper because the applied references are so related that the appearance of features shown in one would suggest the application of those features to the other. See In re Rosen, 673 F.2d 388, 213 USPQ 347 (CCPA 1982); In re Carter, 673 F.2d 1378, 213 USPQ 625 (CCPA 1982), and In re Glavas, 230 F.2d 447, 109 USPQ 50 (CCPA 1956). Further, it is noted that case law has held that a designer skilled in the art is charged with knowledge of the related art; therefore, the combination of old elements, herein, would have been well within the level of ordinary skill. See In re Antle, 444 F.2d 1168,170 USPQ 285 (CCPA 1971) and In re Nalbandian, 661 F.2d 1214, 211 USPQ 782 (CCPA 1981). The combination of references would not change the principle of operation of the prior art invention being modified, hence the teachings of the references are sufficient to render the claims obvious. For the reasons of record and cited herein, the rejection is maintained.
Skog teaches assaying surface antigens, molecules and biomarkers on microvesicles isolated from a blood sample, see sections 0010 and 0011; and page 6, sections 0119 and 0122. “[M]icrovesicles are secreted by tumor cells and circulating in bodily fluids.”, see section 0114. The biomarker associated with a disease is nucleic, see section 0014.
The assayed biomarkers are synaptic vesicle glycoprotein 2A (SV2A) on page 79, 2nd column; sulfatase 2 (SULF2) on page 79, 2nd column and page 88, 1st column; and cell adhesion associated oncogene regulated (CDON) on page 82, 1st column.
Skog does not teach the gene expression product measured is a polypeptide.
However, Pawlowski teaches assessing circulating structures for surface proteins and/or biomarkers within blood for analysis of cancers including pancreatic cancer, see abstract; page 2, section 0010; page 4, section 0021; page 4, section 0017; page 5, section 0024; page 11, section 0054; page 14, section 0064; page 44, section 00188; page 45, section 00194; page 63, section 00271; and page 166, section 00610.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to assay for multiple gene expression products as taught by all references, herein.
Moreover, one of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success exemplified in all prior art documents, wherein numerous gene products that are polypeptides have been isolated, identified and measured within blood successfully, see all documents in their entirety.
Conclusion
14. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
15. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
18 June 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
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