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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13 and 19-21, in the reply filed on 9/4/2026 is acknowledged.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 9/8/2023 and 9/4/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 2 objected to because of the following informalities: it is recommended that "said guiding structure". Appropriate correction is required.
Claim objected to because of the following informalities: it is recommended that "said guiding structure". Appropriate correction is required.
Claim objected to because of the following informalities: it is recommended that ". Appropriate correction is required.
Claim objected to because of the following informalities: it is recommended that "said guiding structure" . Appropriate correction is required.
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.
Claims 1, 4-5, and 9-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murphy et al. (EP 2057277) (already of record).
Regarding claim 1, Murphy et al. discloses a gradient-on-a-chip device for quantification of cell migration (para. 0018 “quantification of… cell migration”) and metastatic potential of tumor cells (para. 0004 “metastasis”), said device comprising:
- a chip having a chip surface (Fig. 48 assay substrate holder 100);
- a nano gradient layer of nanoparticles provided on said chip surface, said nano gradient layer having a gradient direction along an axis of an X-Y plane of said chip surface (Fig. 48; paras. 0166 “surfaces that have particles (nano- to micro-sized particles distributed thereon)”; 0296 “gradient of topographies across its surface”); and
- biomolecules conjugated to said nanoparticles (para. 0199 “a recognition moiety can be attached to the surface of a SAM (self-assembled monolayer)”; para. 0232 “the recognition moiety may be a biomolecule”) by means of a linker linking together said biomolecule to said nanoparticles (para. 0232 “antigen binding protein”);
wherein said chip surface having at least one guiding structure arranged to guide said tumor cells in said gradient direction, said guiding structure extending in said gradient direction and delineating a migration corridor comprising said nano gradient layer (para. 0167 “hydrophobic stamp containing topography”; Fig. 48 coated surface 700).
Regarding claim 4, Murphy et al. discloses a gradient-on-chip device wherein said guiding structure extends continuously along said chip surface (para. 0167 “hydrophobic stamp containing topography”).
Regarding claim 5, Murphy et al. discloses a gradient-on-chip device wherein said migration corridor has a substantially constant width along its extension direction (Fig. 48; para. 0432 “width of 200 nm”).
Regarding claim 9, Murphy et al. discloses a gradient-on-chip device wherein said linker comprises the linker complex biotin/streptavidin (para. 0232 “biotin”).
Regarding claim 10, Murphy et al. discloses a gradient-on-chip device wherein the chip surface between the nanoparticles at least partly is coated by a coating agent (para. 0305 “coated surface”).
Claim Rejections - 35 USC § 103
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 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.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Hayden et al. (US 2014/0159714 A1).
Regarding claim 2, Murphy et al. discloses a gradient-on-a-chip device comprising a guiding structure (para. 0167 “hydrophobic stamp containing topography”), but does not disclose wherein said guiding structure is a ridge extending out of said chip surface. However, Hayden et al. teaches guiding ridges (abstract “12”) which exert mechanical force on cells and displace the cells to a desired region of the device (para. 0041). It would have been obvious to a person of ordinary skill in the art to use the Hayden et al. configuration of guiding ridges in Murphy et al.’s device with a reasonable expectation that they would exert mechanical force on cells and displace the cells to a desired region of the device. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Hayden et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Hayden et al. to obtain the invention as specified in claim 2.
Regarding claim 3, Murphy et al. discloses a gradient-on-chip device wherein said device further comprises a chip surface area void of nano gradient layer (Fig. 48 coated surface 700), but does not disclose wherein said guiding structure is the boundary line between said migration corridor and said chip surface area void of nano gradient layer. However, Hayden et al. teaches guiding ridges (abstract “12”) which exert mechanical force on cells and displace the cells to a desired region of the device (para. 0041). It would have been obvious to a person of ordinary skill in the art to use the Hayden et al. configuration of guiding ridges in Murphy et al.’s device with a reasonable expectation that they would exert mechanical force on cells and displace the cells to a desired region of the device. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Hayden et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Hayden et al. to obtain the invention as specified in claim 3.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record).
Regarding claim 6, Murphy et al. discloses a gradient-on-chip device comprising a migration corridor having a width of 200 nm (para. 0432), but does not explicitly disclose a width in the range of 20 to 500 µm. However, it has been held that in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists (MPEP § 2144.05). The claimed range is obvious in view of Murphy et al. because Murphy et al. discloses a width of 200 nm, which overlaps the claimed range of 20 to 500 µm. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the claimed range from the broader prior art range because the prior art teaches the same utility over the entire range.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Yanik et al. (US 2020/0378925 A1).
Regarding claim 7, Murphy et al. discloses a gradient-on-chip device comprising a migration corridor (Fig. 48 coated surface 700), but does not disclose wherein said migration corridor is 1 to 20 mm long. However, Yanik et al. teaches a channel length of 1 mm to 5 mm (para. 0071) which allows the device to generate a vertical acoustic force (para. 0071) to push particles of interest to a desired location (para. 0072). It would have been obvious to a person of ordinary skill in the art to use the Yanik et al. configuration of a channel length of 1 mm to 5 mm in Murphy et al.’s device with a reasonable expectation that it would generate a vertical acoustic force to push particles of interest to a desired location. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Yanik et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Yanik et al. to obtain the invention as specified in claim 7.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Cox (US 2018/0236442 A1) (already of record).
Regarding claim 8, Murphy et al. discloses a gradient-on-chip device comprising a migration corridor (Fig. 48 coated surface 700), but does not disclose said wherein device comprises two or more migration corridors. However, Cox teaches multiple migration lanes (Fig. 1; para. 0138) which allows a user to assess cell migration in response to multiple factors (abstract; Fig. 1). It would have been obvious to a person of ordinary skill in the art to use the Cox configuration of multiple migration lanes in Murphy et al.’s device with a reasonable expectation that it would allow a user to assess cell migration in response to multiple factors. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Cox. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Cox to obtain the invention as specified in claim 8.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Motamedi et al. (US 2020/0300849 A1).
Regarding claim 11, Murphy et al. discloses a gradient-on-chip device comprising nanoparticles (para. 0166 “surfaces that have particles (nano- to micro-sized particles distributed thereon)”), but does not explicitly disclose nanoparticles having a diameter in the range of 1 to 100 nanometers (nm). However, Motamedi et al. teaches nanoparticles with a diameter of about 1 nm to about 100 nm (para. 0055) and an iron core (para. 0056) which contains the same or greater magneticity as larger iron oxide nanoparticles (para. 0056). It would have been obvious to a person of ordinary skill in the art to use the Motamedi et al. configuration of nanoparticles with a diameter of about 1 nm to about 100 nm in Murphy et al.’s device with a reasonable expectation that nanoparticles of this size with an iron core would contain the same or greater magneticity as larger iron oxide nanoparticles. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Motamedi et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Motamedi et al. to obtain the invention as specified in claim 11.
Regarding claim 12, Murphy et al. discloses a gradient-on-chip device comprising nanoparticles, but does not disclose wherein said nanoparticles are gold particles. However, Motamedi et al. teaches gold nanoparticles (para. 0055) with an iron core (para. 0056) which contains the same or greater magneticity as larger iron oxide nanoparticles (para. 0056). It would have been obvious to a person of ordinary skill in the art to use the Motamedi et al. configuration of gold nanoparticles in Murphy et al.’s device with a reasonable expectation that gold nanoparticles with an iron core would contain the same or greater magneticity as larger iron oxide nanoparticles. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Motamedi et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Motamedi et al. to obtain the invention as specified in claim 12.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Nordon et al. (US 2022/0204903 A1).
Regarding claim 13, Murphy et al. discloses a gradient-on-chip device comprising a migration corridor (Fig. 48 coated surface 700), but does not disclose wherein said device further comprises two or more migration corridors provided on top of each other. However, Nordon et al. teaches stacked channels (para. 0150) which allows each channel in the stack to be supplied by a single source (para. 0150). It would have been obvious to a person of ordinary skill in the art to use the Nordon et al. configuration of stacked channels in Murphy et al.’s device with a reasonable expectation that they would allow each channel in the stack to be supplied by a single source. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Nordon et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Nordon et al. to obtain the invention as specified in claim 13.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Salmanzadeh et al. (US 12,186,751).
Regarding claim 19, Murphy et al. discloses a gradient-on-chip device comprising a guiding structure (para. 0167 “hydrophobic stamp containing topography”), but does not disclose wherein said guiding structure is a recession pointing into said chip surface. However, Salmanzadeh et al. teaches that channels etched into the surface of a chip is known in the art (Col. 43, line 10). Though Murphy et al. does not explicitly teach a channel etched into the chip surface, it would have been obvious to a person of ordinary skill in the art to use an etched channel because the substitution of one known element for another would have predictably resulted in a channel that guides particles and cells along a path, with reasonable expectation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the teachings of Murphy et al. with the teachings of Salmanzadeh et al. to obtain the invention as specified in claim 19.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Yanik et al. (US 2020/0378925 A1) as applied to claim 7 above, and further in view of Cox (US 2018/0236442 A1) (already of record).
Regarding claim 20, Murphy et al. discloses a gradient-on-chip device comprising a migration corridor (Fig. 48 coated surface 700), but does not disclose wherein said migration corridor has a length:width ratio of 200:1 to 20:1. However, Cox teaches migration lanes comprising a width from about 1 µm to about 1350 µm and a length of about 1 mm to about 50 mm (para. 0138) which allows cells to migrate along a gradient (para. 0071). It would have been obvious to a person of ordinary skill in the art to use the Cox configuration of a width from about 1 µm to about 1350 µm and a length of about 1 mm to about 50 mm in modified Murphy et al.’s device with a reasonable expectation that it would allow cells to migrate along a gradient. This method for improving modified Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Cox. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Murphy et al. and Cox to obtain the invention as specified in claim 20.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (EP 2057277) (already of record) in view of Beaumont et al. (US 11,666,913).
Regarding claim 21, Murphy et al. discloses a gradient-on-chip device comprising a coated surface (Fig. 48 coated surface 700), but does not explicitly disclose wherein the coating agent is ECM fibers. However, Beaumont et al. teaches an extracellular matrix coating (Col. 38, line 10) which optimizes cell adhesion and fosters cell growth (Col. 38, line 11). It would have been obvious to a person of ordinary skill in the art to use the Beaumont et al. configuration of gold nanoparticles in Murphy et al.’s device with a reasonable expectation that gold nanoparticles with an iron core would contain the same or greater magneticity as larger iron oxide nanoparticles. This method for improving Murphy et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Beaumont et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Murphy et al. and Beaumont et al. to obtain the invention as specified in claim 21.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Yung et al. (US 2013/0157283 A1) discloses a microfluidic device for detecting pathogens including nanoparticles migrating across a gradient of magnetic fields.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY LOPEZLIRA whose telephone number is (703)756-5517. The examiner can normally be reached Mon - Fri: 8:30-5:00.
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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