Patent Application 17773774 - BIOCHIP HAVING MICROCHANNEL PROVIDED WITH - Rejection

Patent Application 17773774 - BIOCHIP HAVING MICROCHANNEL PROVIDED WITH

Title: BIOCHIP HAVING MICROCHANNEL PROVIDED WITH CAPTURING AGENT FOR PERFORMING CYTOLOGICAL ANALYSIS

Application Information

• Invention Title: BIOCHIP HAVING MICROCHANNEL PROVIDED WITH CAPTURING AGENT FOR PERFORMING CYTOLOGICAL ANALYSIS
• Application Number: 17773774
• Submission Date: 2025-04-10T00:00:00.000Z
• Effective Filing Date: 2022-05-02T00:00:00.000Z
• Filing Date: 2022-05-02T00:00:00.000Z
• National Class: 435
• National Sub-Class: 007250
• Examiner Employee Number: 89199
• Art Unit: 1677
• Tech Center: 1600

Rejection Summary

• 102 Rejections: 1
• 103 Rejections: 0

Cited Patents

The following patents were cited in the rejection:

• US 0404334🔗

Office Action Text

    DETAILED ACTION
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 .
Status of Claims
Claims 1-24 are pending and examined.
Priority
This application 17/773,774 (PGPub: US2022/0404334) was filed 05/02/2022. This application is a 371 of PCT/US2020/058272 filed 10/30/2020, which claims benefit of US Provisional Application 62/928,109 filed 10/30/2019, 62/989,360 filed 03/13/2020, 63/037,287 filed 06/10/2020, 63/043,536 filed 06/24/2020, 63/049,443 filed 07/08/2020, and 63/072,502 filed 08/31/2020.
Information Disclosure Statement
The Information Disclosure Statements filed 08/11/2022, 01/29/2024 and 04/29/2024 have been considered by the Examiner.
Claim Objections
Claim 2-3, 5-11, 14 and 17 are objected to because of the following informalities: 
Claims 2-3, 5-10, 14 and 17 should recite “wherein” after the preamble.
Claim 11 at lines 2-4 recites “…a reservoir that is in fluid communication the at least one microchannel, reservoir including…” and should be corrected to recite “…a reservoir that is in fluid communication with the at least one microchannel, the reservoir including a blood sample and the pressure pump configured to provide pressure to the reservoir…”
Claim 14 should include “a” or “the” in front of the term “viscosity” (while ensuring there is proper antecedent basis). 
Appropriate correction is required.
Claim Rejections - 35 USC § 112
	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.


Claims 8-10, 15 and 24 are 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.
	Claim 8 is indefinite because it recites “the shear stress” and this limitation lacks antecedent basis.
	Claim 9 is indefinite because it recites “each microchannel”, however claim one has only recited “at least one microchannel” and not limited the claim to including additional microchannels such that the term “each” would be necessary.
	Claim 10 is indefinite because it recites “the cross-linker” and this limitation lacks antecedent basis.
	Claim 15 is unclear because it recites “the endothelial cells are provided in the at least one microchannel by culturing the endothelial on a fibronectin coated surface of the microchannel under continuous flow of the culture medium” and based on the process given in the claim, it is unclear if this step is intending to limit the capturing agent or an additional culturing step for the system.
	Claim 24 is unclear because it recites “the endothelial cells are provided in the at least one microchannel by culturing the endothelial on a fibronectin coated surface of the microchannel under continuous flow of the culture medium” and based on the process given in the claim, it is unclear if this step is intending to limit the capturing agent or an additional culturing step for the method.
Claim Rejections - 35 USC § 112
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.

Claim 19 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.  
Claim 19 recites that the fluid sample is perfused through the microchannel at a physiologically relevant shear stress value, however, claim 16 has already stated this limitation and thus claim 19 fails to further limit the claim from which it depends.
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
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) 1-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gurkan et al., WO 2018/170412 (Pub Date: 09/20/2018, hereinafter “Gurkan” IDS).
 	Regarding claim 1, Gurkan teaches throughout the publication a microfluidic system for measuring cell adhesion (paragraph 0007), the system comprising: 
a gas impermeable housing including at least one microchannel defining at least one cell adhesion region (paragraphs 0012 and 0082), the at least one cell adhesion region being provided with at least one capturing agent that adheres a cell of interest to a surface of the at least one microchannel when a fluid sample containing cells is passed through the at least one microchannel (paragraphs 0083 and 0091), wherein at least the capturing agent includes at least one of E- Selectin, P-Selectin, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1) or endothelial cells functionalized to the surface of the microchannel (paragraphs 0079, 0110 and 0221); and 
an imaging system for measuring the adherence of cells of interest adhered by the at least one capturing agent to the surface of the at least one microchannel when the fluid sample is passed therethrough (paragraph 0127).
Regarding claim 2, Gurkan teaches they system wherein the at least one microchannel comprising multiple microchannels, the microchannels being fluidly isolated from each other (paragraphs 0078).
Regarding claim 3, Gurkan teaches the system wherein the fluid comprising blood and the cells of interest being red blood cells (paragraph 0008).
Regarding claim 4, Gurkan teaches the system further comprising a micro-gas exchanger for controlling the oxygen content of the blood prior to delivering the blood to the at least one microchannel (see reference claim 4).
Regarding claim 5, Gurkan teaches the system wherein the micro-gas exchanger providing hypoxic blood to the at least one microchannel (see reference claim 5).
Regarding claim 6, Gurkan teaches the system wherein the at least one microchannel having a width that continuously changes in a direction of fluid flow therethrough (see reference claim 6).
Regarding claim 7, Gurkan teaches the system wherein the microchannel having a convergent and divergent cross-sectional area along the direction of flow (see reference claim 7).
Regarding claim 8, Gurkan teaches the system wherein the shear stress on fluid flowing through the microchannel decreasing along the length of the microchannel (see reference claim 8).
Regarding claim 9, Gurkan teaches the system wherein the capturing agent being covalently immobilized to surfaces of each microchannel with a cross-linker (see reference claim 9).
Regarding claim 10, Gurkan teaches the system wherein the cross-linker being GMBS (paragraph 0125).
Regarding claim 11, Gurkan teaches the system further including a pressure pump and a reservoir that is in fluid communication the at least one microchannel, reservoir including a blood sample and the pressure pump configured to provide pressure to reservoir such that the blood sample flows through the at least one microchannel at a physiologically relevant shear stress value (paragraph 0224).
Regarding claim 12, Gurkan teaches the system wherein the physiologically relevant shear stress value is about 0.5 dyne/cm2 to about 1 dyne/cm2 (paragraph 0224).
Regarding claim 13, Gurkan teaches the system wherein the imaging system includes a control unit for determining viscosity of the fluid sample (paragraph 0170).
Regarding claim 14, Gurkan teaches the system wherein viscosity of the fluid sample is determined by measuring the mean flow velocity of the fluid sample as it passes through the microchannel (paragraph 0045, 0175 and 0177).
Regarding claim 15, Gurkan teaches the system wherein the endothelial cells are provided in the at least one microchannel by culturing the endothelial on a fibronectin coated surface of the microchannel under continuous flow of the culture medium through the at least one microchannel (paragraphs 0079, 0106, 0110, 0113 and for example claims 9 and 23).
	Regarding claim 16, Gurkan teaches throughout the publication methods and systems comprising: 
providing a gas impermeable housing including at least one microchannel defining at least one cell adhesion region (paragraphs 0012 and 0082), the at least one cell adhesion region being provided with at least one capturing agent that adheres a cell of interest to a surface of the at least one microchannel when a fluid sample containing cells is passed through the at least one microchannel (paragraphs 0083 and 0091), wherein at least the capturing agent includes at least one of E- Selectin, P-Selectin, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1) or endothelial cells functionalized to the surface of the microchannel (paragraphs 0079, 0110 and 0221); 
perfusing a fluid sample containing the blood cells through the at least one microchannel at a physiologically relevant shear stress rate (paragraph 0224); and 
measuring adherence of the blood cells to the at least one capturing agent when the fluid sample is passed therethrough (paragraph 0127).
Additionally, Gurkan teaches that the biochip device can be used to analyze adhesive properties of RBCs and WBCs that can be used to monitor disease severity, treatment response sand treatment effectiveness in a clinically meaningful way (paragraphs 0078 and 0098). More specifically, Gurkan teaches the device and imaging system can quantify the adhered cells in each channel to measure the efficacy of a therapeutic treatment administered to a subject from which the cells are obtained (paragraph 0103), which reads on the limitations of measuring efficacy of therapeutic agent that is added to at least the fluid sample prior to perfusion through the at least one microchannel since the therapeutic treatment is added to the fluid sample through administration to the patient and therefore before perfusion through the microchannel.
	Regarding claim 17, Gurkan teaches the method wherein the fluid sample comprises blood and the cells being red blood cells and/or white blood cells (see reference claim 3).
Regarding claim 18, Gurkan teaches the method wherein the adherence of the blood cells is measured under at least one normoxic or hypoxic conditions (paragraph 0200).
Regarding claim 19, Gurkan teaches the method wherein the fluid sample is perfused through the microchannel at a physiologically relevant shear stress value (paragraph 0224).
Regarding claim 20, Gurkan teaches the method wherein the physiologically relevant shear stress value is about 0.5 dyne/cm2 to about 1 dyne/cm2 (paragraph 0224).
Regarding claim 21, Gurkan teaches the method wherein the adherence of the blood cells is measured using an imaging system (see reference claim 1).
Regarding claim 22, Gurkan teaches the method wherein the imaging system includes a control unit for determining viscosity of the fluid sample (paragraph 0170).
Regarding claim 23, Gurkan teaches the method wherein viscosity of the fluid sample is determined by measuring the mean flow velocity of the fluid sample as it passes through the microchannel (paragraphs 0045, 0175 and 0177).
Regarding claim 24, Gurkan teaches the method wherein the endothelial cells are provided in the at least one microchannel by culturing the endothelial on a fibronectin coated surface of the microchannel under continuous flow of the culture medium through the at least one microchannel (paragraphs 0079, 0106, 0110, 0113 and for example claims 9 and 23).

Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA  as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). 
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1, 4-5 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5 and 16 of copending Application No. 16/493,561 (reference application). 
Although the claims at issue are not identical, they are not patentably distinct from each other because, regarding instant claim 1, application 561 recites a microfluidic biochip device comprising: a housing including at least one microchannel defining at least one cell adhesion region, the at least one cell adhesion region being provided with at least one capturing agent covalently immobilized to a surface of the at least one microchannel with a cross-linker, the at least one capturing agent adheres red blood cells of interest in a fluid sample containing blood to the surface of the at least one microchannel when the fluid sample containing blood is continuously passed through the at least one microchannel, the at least one microchannel including a variable width microchannel having both a convergent and divergent cross-sectional area along the direction of flow such that the fluid sample containing blood experiences a continuously variable shear rate gradient during constant continuous flow through the variable width microchannel, wherein the divergent cross-sectional area is positioned between an inlet port of the variable width microchannel for receiving the fluid sample and the convergent cross-sectional area and the variable width microchannel has a width that increases in the divergent cross-sectional area such that mean flow velocity and shear stress of the fluid sample decreases along the length of flow while a flow rate of the fluid sample is constant, wherein the at least one microchannel is configured to simulate physiological shear rate gradients of microcirculatory blood flow at a constant single volumetric flow of the fluid sample containing blood; and an imaging system configured to measure the morphology and/or quantity of red blood cells of interest adhered by the at least one capturing agent to the surface of the at least one microchannel at variable shear rate gradients when the fluid sample containing blood is continuously passed therethrough (see reference claim 1).
Additionally, reference claim 4 reads on instant claim 4, reference claim 5 reads on instant claim 5 and reference claim 16 reads on instant claim 10.

This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.

Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677