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 .
Specification
The objection to the specification is withdrawn in light of the amendment.
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.
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 nonobviousness.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Cushing (“Reducing WBC background in cancer cell separation products by negative acoustic contrast particle immuno-acoustophoresis”) (previously cited) in view of Ward (US 20090029870) (previously cited) and Grenvall (“Concurrent Isolation of Lymphocytes and Granulocytes Using Prefocused Free Flow Acoustophoresis”) (previously cited).
Regarding claim 17, Cushing discloses a system, comprising:
an acoustophoresis device (pg. 258, under “2.1. Manufacturing of acoustophoresis chip & instrument setup”, “acoustophoresis chip”) comprising a first microfluidic channel (annotated Fig. 1), the first microfluidic channel having a first outlet (annotated Fig. 1) defined between a pair of second outlets (annotated Fig. 1), the acoustophoresis device configured to:
receive, via the first microfluidic channel (annotated Fig. 1), a first solution (pg. 258, under “2.4. Healthy blood donor and cell preparations”, “washing buffer”; pg. 258, under “2.6. Activated EPs capture WBCs in an RBC-lysed sample”, “washing buffer”) including a first target particle (Fig. 2, “WBCs” a white blood cell, or pg. 258, under “2.4. Healthy blood donor and cell preparations”, “viable WBCs”), a second target particle (pg. 258, under “2.5. Cell culture, immunostaining and spiking”, “MCF-7 (breast cancer)” and “DU-145 (prostate cancer)”), and a first selection particle (pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”, “EPs with streptavidin conjugated anti-CD45 monoclonal antibodies for capturing non-fixed WBCs”), the first solution having been incubated such that the first target particle is bound to the first selection particle (Fig. 3b, pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”, “EPs with streptavidin conjugated anti-CD45 monoclonal antibodies for capturing non-fixed WBCs”) in the first solution such that a net acoustic contrast of a complex of the first target particle and the first selection particle differs from an acoustic contrast of the second target particle (Fig. 2; pg. 257, under “Introduction”, right column, “positive contrast properties of cells to a negative acoustic contrast complex using negative contrast particles” was used both in the background art and in this reference, see pg. 263 under “4. Conclusions”, “non-fixed cancer cells by negative selection of WBCs”);
perform acoustophoresis in the first microfluidic channel (annotated Fig. 1 and Fig. 2);
provide, via the first outlet (annotated Fig. 1 and Fig. 2), a first output stream (annotated Fig. 1 and Fig. 2) comprising the first target particle (Fig. 2, “WBCs” a white blood cell) bound to the first selection particle (pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”);
provide, via the pair of second outlets (annotated Fig. 1 and Fig. 2), a second output stream (annotated Fig. 1 and Fig. 2) comprising the second target particle (pg. 258, under “2.5. Cell culture, immunostaining and spiking”, “MCF-7 (breast cancer)” and “DU-145 (prostate cancer)”).
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Cushing, Annotated Fig. 1
Cushing does not disclose:
a second microfluidic channel … the second microfluidic channel having a first inlet defined between a pair of second inlets
a second selection particle
provide, via … the pair of second inlets of the second microfluidic channel, a first output stream
receive, via the first inlet of the second microfluidic channel, a second solution to modify a density and a compressibility of the first output stream within the second microfluidic channel; and
perform acoustophoresis in the second microfluidic channel.
Regarding feature 2, Ward discloses:
a second selection particle (paragraph [0012]).
In the analogous art of particle analyzing systems using acoustic radiation pressure, it would have been obvious to one skilled in the art before the effective filing date to modify the acoustophoresis device of Cushing with the second selection particle of Ward in order to bind to a specific subset of the population of particles (Ward, paragraph [0012]).
Additionally, regarding the limitation “a second selection particle”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B).
Regarding features 1 and 3-5, Grenvall discloses:
a second microfluidic channel (annotated Fig. 1d) … the second microfluidic channel having a first inlet (annotated Fig. 1d) defined between a second inlet (annotated Fig. 1d)
provide, via … the second inlet (annotated Fig. 1d) of the second microfluidic channel (annotated Fig. 1d), a first output stream (annotated Fig. 1d)
receive, via the first inlet (annotated Fig. 1d) of the second microfluidic channel (annotated Fig. 1d), a second solution (pg. 5597, right col. “flow media including water”; pg. 5598, left col.; pg. 5599 “sheath fluid”; and caption to Fig. 1) to modify a density and a compressibility of the first output stream (pg. 5597, right col. “flow media including water”) within the second microfluidic channel (annotated Fig. 1d); and
perform acoustophoresis (pg. 5598, right col.; annotated Fig. 1d and associated caption) in the second microfluidic channel (annotated Fig. 1d).
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Grenvall, annotated Fig. 1d
In the analogous art of free flow acoustophoresis, it would have been obvious to one skilled in the art before the effective filing date to modify modified Cushing to have a second microfluidic channel with a first inlet, a second inlet, a first output stream, a second solution, and acoustophoresis in order to fractionate leukocytes or other complex particle- or biosuspensions into pure subpopulations with multiple target outlets (Grenvall; pg. 5596, left col.); and, for example, accomplish this fractionation for the isolation of different leukocyte subpopulations to analyze gene expression, interleukin signaling between different subpopulations during immune responses, and to detect viral, bacterial, and cancerous diseases (pg. 5596, right col.).
Regarding the limitation “a pair of second inlets”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify a second inlet of modified Cushing with a pair of second inlets in order to have a sheath flow in the center of the pair of second inlet fluid flows to increase the population of particles being sorted over time with two second inlets instead of one second inlet.
Regarding the limitations of claim 17, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Cushing would be fully capable of operating in this manner given the acoustophoresis device comprising microfluidic channels.
Regarding the limitations of claim 17 after the phrase “the acoustophoresis device configured to”, the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115.
Regarding claim 18, Cushing discloses further comprising a container (Fig. 1, second container from the left “Cell Mixture w/ Activated EPs”) comprising incubation media (pgs. 258-259, under “2.6. Activated EPs capture WBCs in an RBC-lysed sample”, “washing buffer” and under “2.7. Enrichment of cancer cells using activated EPs with acoustophoresis”, “samples were incubated at RT”) including the first selection particle (pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”, “EPs with streptavidin conjugated anti-CD45 monoclonal antibodies for capturing non-fixed WBCs”), the first target particle (Fig. 2, “WBCs” a white blood cell, or pg. 258, under “2.4. Healthy blood donor and cell preparations”, “viable WBCs”), and the second target particle (pg. 258, under “2.5. Cell culture, immunostaining and spiking”, “MCF-7 (breast cancer)” and “DU-145 (prostate cancer)”), such that the first selection particle (pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”, “EPs with streptavidin conjugated anti-CD45 monoclonal antibodies for capturing non-fixed WBCs”) bind to the first target particle in the incubation media (pg. 260, “3.3. Activation of EPs with anti-CD45 antibody”).
Cushing does not disclose the second selection particle.
Ward discloses:
a second selection particle (paragraph [0012]).
In the analogous art of particle analyzing systems using acoustic radiation pressure, it would have been obvious to one skilled in the art before the effective filing date to modify the acoustophoresis device of Cushing with the second selection particle of Ward in order to bind to a specific subset of the population of particles (Ward, paragraph [0012]).
Additionally, regarding the limitation “a second selection particle”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B).
Regarding claim 19, Cushing discloses wherein the container (Fig. 1, second container from the left “Cell Mixture w/ Activated EPs”) is fluidly coupled (Fig. 1) to an inlet (Fig. 1, “Center Inlet”) of the first microfluidic channel (pg. 258, under “2.1. Manufacturing of acoustophoresis chip & instrument setup”, “the microchannel”) of the acoustophoresis device (pg. 258, under “2.1. Manufacturing of acoustophoresis chip & instrument setup”, “acoustophoresis chip”), and the incubation media (pgs. 258-259, under “2.6. Activated EPs capture WBCs in an RBC-lysed sample”, “washing buffer” and under “2.7. Enrichment of cancer cells using activated EPs with acoustophoresis”, “samples were incubated at RT”) is provided at least as part of the first solution (Fig. 1, “Cell Mixture w/ Activated EPs”) to the first microfluidic channel (pg. 258, under “2.1. Manufacturing of acoustophoresis chip & instrument setup”, “the microchannel”) of the acoustophoresis device (pg. 258, under “2.1. Manufacturing of acoustophoresis chip & instrument setup”, “acoustophoresis chip”).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Piyasena (US 20180264482) (newly cited) – This invention is about the separation of nanoparticles via acoustofluidic flow relocation.
Fiering (US 20180313816) (newly cited) – This invention, by the Applicant, is about acoustic separation of particles for bioprocessing.
Fiering (US 20180361053) (newly cited) – This invention, by the Applicant, is about an acoustophoresis device having improved dimensions.
Fiering (US 20190290829) (newly cited) – This invention, by the Applicant, is about acoustic separation for bioprocessing.
Fiering (US 20190307946) (newly cited) – This invention, by the Applicant, is about acoustic separation for bioprocessing.
Fiering (US 20200057045) (newly cited) – This invention, by the Applicant, is about acoustic separation for bioprocessing.
Yen (US 20220072548) (newly cited) – This invention is about a microfluidic chip for acoustic separation of biological objects.
Laurell (US 20140231315) (newly cited) – This invention is a system and method to separate cells and/or particles.
Response to Arguments
Applicant’s arguments filed 10/21/2025 have been fully considered but they are not persuasive.
Regarding Applicant arguments, pg. 9 of 11, modified Cushing in view of Grenvall teaches a second microfluidic channel that receives a stream and performs acoustophoresis. It is obvious for this to occur due to the reasons set above. The combination teaches the limitation. 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).
Regarding Applicant arguments, pgs. 9-10 of 11, Grenvall discloses one additional inlet and several outlets, as Applicant has noted. However, multiple additional inlet channels, such as the pair of second inlets, accomplishing the same task is considered obvious under duplication of parts, see above.
Two solutions are cited between Cushing (Cushing, pgs. 258-259, under “2.6. Activated EPs capture WBCs in an RBC-lysed sample”, “washing buffer” and under “2.7. Enrichment of cancer cells using activated EPs with acoustophoresis”, “samples were incubated at RT”) and Grenvall (Grenvall, pg. 5597, right col. “flow media including water”; pg. 5598, left col.; pg. 5599 “sheath fluid”; and caption to Fig. 1), so a second solution is taught.
Lastly, regarding the limitations, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Cushing would be fully capable of operating in this manner given the cited microfluidic structures. Modified Cushing (in view of Grenvall) also has multiple acoustophoresis sites to achieve the intended use and manner of operation of the device.
Regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799