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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 13, 2026 has been entered.
3. Claims 1, 4, 21, 22, 25, 26, 37 and 38 are pending.
Claims 2, 3, 12-20, 23 and 24 have been cancelled.
Claims 1, 26, 37 and 38 have been amended.
Claims 1, 4, 21, 22, 25, 26, 37 and 38 are examined on the merits.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 102
4. The rejection of claim(s) 37 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 (Journal of Clinical Ligand Assay 25 (1): 104-110, Spring 2002) is withdrawn in light of Applicant’s amendment to claim 37 limiting the expression product to a polypeptide. Claim 2 has been cancelled.
5. The rejection of claim(s) 37 under 35 U.S.C. 102(a)(1) as being anticipated by Pawlowski et al., WO 2012/170711 A1 (published 13 December 2012), as evidenced by Kagan et al. (Journal of Clinical Ligand Assay 25 (1): 104-110, Spring 2002) is withdrawn in light of Applicant’s amendment to the claim deleting polypeptide expression product of surface protein genes, integrin subunit alpha 6 (ITGA6) and tissue inhibitor of metallopeptidase 2 (TIMP2).
Claim Rejections - 35 USC § 103
6. 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), 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US 2011/0256155 A1 (published October 20, 2011) and Pawlowski et al., WO 2012/170711 A1 (published 13 December 2012) is withdrawn in light of the deletion of polypeptide expression products of surface protein genes, interleuickin 6 cytokine family signal transducer (IL6ST); arylsufatase A (ARSA); tissue inhibitor of metallopeptidase 2 (TIMP2); and integrin subunit alpha 6 (ITGA6), see Amendments to the Claims submitted January 13, 2026, page 3. Claims 2, 3, 23 and 24 have been cancelled.
New Objections
Claim Objections
7. Claim 26 is objected to because of the following informality: it depends from a cancelled claim.
Correction is required.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
9. Claim 26 is rejected 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.
a. Claim 26 cites “…the at least one classical circulating tumor is a pancreatic cancer classical circulating tumor cell”. A tumor is art known to be an abnormal mass or clump of uncontrollably dividing cells and not just one cell. Hence, the claim language is incongruent.
10. Claim 26 recites the limitation "the at least one classical circulating tumor" spanning lines 1 and 2. There is insufficient antecedent basis for this limitation in the claim.
11. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
12. Claim 25 is rejected 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. These claims depend from independent claim 1, which cites three expression products, SV2A, SULF2 and CDON. However, claim 25 cites four additional expression products. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
13. 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.
14. 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.
15. 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 maintained. Claim 2 has been cancelled.
Applicant states with the amendment to claim 1 reciting the limitations of cancelled claim 3, the claim is novel and the instant rejection is obviated, see Remarks submitted January 13, 2026, page 4, last full paragraph (para.).
Applicant’s arguments and noted passages within Skog have been carefully considered and found unpersuasive.
As stated herein, Skog does isolate a blood sample and the classical circulating tumor cells therein utilizing size exclusion chromatography. Size exclusion chromatography is art known to be a technique for hydrodynamic size-based separation. Accordingly, the rejection is maintained.
Skog discloses isolation methods and techniques that must be performed prior to the assessment of the surface antigens, see sections 0118-0129 spanning pages 6 and 7; and claims 10, 14, 26, 30, 41, 45, 60 and 64 spanning pages 106-108. As cited in Skog’s claims, a biological sample is provided, then the isolation of the samples via size exclusion chromatography and lastly quantification, determining and/or measuring the amount of nucleic acid within the sample.
Skog discloses 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.
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.
Assayed blood samples are obtained from individuals with pancreatic cancer. Thereby the classical circulating tumor cell within the blood sample comprising the cells are assayed using the disclosed size exclusion chromatography (SEC), see page 2, sections 0012-0016 and 0020; and claims 10, 14, 26, 30, 41, 45, 60 and 64 spanning pages 106-108. SEC is art known to be a specific type of hydrodynamic size-based separation.
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.
16. Claim(s) 37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Okada et al., US 2009/0253147 A1 (published October 8, 2009). Okado discloses cell adhesion associated oncogene regulated (CDON) is expressed on stem cells, see page 1, section 0006. Biological samples including blood was assayed for CDON, see page 5, section 0070; page 6, section 0079; page 7, section 0084; and section 0093 spanning pages 7 and 8.
Claim Rejections - 35 USC § 103
17. 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.
18. 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.
19. The rejection of claim(s) 1, 4, 21, 22, 25, 26 and 38 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. Claims 2, 3, 23 and 24 have been cancelled.
Applicant asserts “Huang is alleged to teach no more than blood collection and processing and does not disclose isolating "by hydrodynamic size-based separation or immunodepletion", as now recited in independent claim 1.
Applicants submit that because Skog and Pawlowski each fail to disclose or suggest the presently claimed invention for at least the reasons discussed above, and because the Huang reference fails to remedy those defects, no combination of Skog, Kagan, Huang, and Pawlowski can render the claimed invention obvious.
In view of the foregoing, Applicants submit that the current claims are not obvious in light of any of the prior art provided.”, see Remarks submitted January 13, 2026, page 5.
These arguments have been carefully considered, but fail to persuade.
Foremost, 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. 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.
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.
20. Claim(s) 37 is rejected 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). 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
21. 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.
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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
22 January 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643