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 .
DETAILED ACTION
Status of Claims
Claims 1-18 and 35-43 are pending and have been examined.
Election/Restriction
Applicant's election without traverse of Group I, claims 1-18 and 35-39, in the reply filed on 10/27/2025 is acknowledged. Applicant cancelled claims 19-34 and amended claims 40-43 to be dependent upon claim 1 and thus Group IV, claims 40-43, has been rejoined and examined. Claims 1-18 and 35-43 encompass the claimed invention and have been examined.
Priority
This application, Serial No. 17/634,533 (PGPub: US2022/0282240) was filed 02/10/2022. This application is a 371 of PCT/US2020/046208 filed 08/13/2020, which claims benefit to Provisional Patent Application 62/886,557 filed 08/14/2019.
Information Disclosure Statements
The Information Disclosure Statement filed 04/19/2022 has been considered by the Examiner.
Claim Objections
Claims 40 and 42 are objected to because of the following informalities:
Claim 40 lines 3-4 recite “a microfluidic device comprising and causing a rare cell” and unless there is structure missing from the claim, the word “comprising” should be removed.
Claim 42 is missing a period at the end of the claim.
Appropriate correction is required.
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.
Claim(s) 1-18 and 35-43 are rejected under 35 U.S.C. 103 as being unpatentable over Allen et al. (US 2018/0106805, Pub Date: 04/19/2018, IDS) in view of Miyake et al. (J. Exp. Med. Volume 172, July 1990, pages 69-75, IDS).
Regarding claims 1 and 7, Allen teaches throughout the publication a biomimetic coating to capture rare cells (paragraphs 0008 and 0009) comprising:
a/b. a plurality of cell capture reagents specific for first and second rare cell surface markers (paragraphs 0008-0009, capture zones contain a plurality of different releasable cell capture reagents; paragraph 0083);
c. a dissolvable matrix (paragraph 0009, releasable capture agents are bound to a dissolvable matrix);
wherein the plurality of different capture molecules are modified to attach to the dissolvable matrix (paragraph 0085), and wherein the dissolvable matrix is attached to a surface (paragraph 0009, releasable capture agents are bound to a dissolvable matrix applied to a nonporous substrate within the capture zone).
While Allen teaches that the plurality of different capture agents specific for first and second surface markers can include antibodies or other bioaffinity moieties (paragraph 0019), the reference fails to teach that one set of plurality of capture agents are cell adhesion molecules comprising hyaluronate.
Miyake teaches throughout the publication that hyaluronate is a potential ligand for CD44 such that adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes (abstract). Additionally, Miyake teaches that hyaluronate could be immobilized for assaying adherence of desired lymphocytes (page 70, Results), as in instant claim 7.
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate as one of the binding agents specific for a cell surface feature of Allen, hyaluronate as taught by Miyake because Allen is generic regarding the types of recognition members that can be incorporated in the capture zone and one skilled in the art would have been motivated to choose the appropriate recognition member based on the desired cell surface feature to be analyzed. One skilled in the art would have had a reasonable expectation of success to incorporate Hyaluronate as taught by Miyake as one of the recognition members in the capture zones of Allen since Allen teaches that antibodies or bioaffinity agents can be used, with CD44 being a desired cell surface marker to analyze (Allen, paragraph 0112) and Miyake teaches that CD44 in cells can recognize and directly bind to hyaluronate (Miyake, page 73, right column, first full paragraph).
Regarding claims 2-3, Allen teaches the coating wherein the plurality of various capture molecules (i.e. capture molecules of Allen and adhesion molecules of Miyake) are modified with a plurality of biotin molecules to attach to a plurality of streptavidin molecules on the dissolvable matrix (paragraph 0085).
Regarding claim 4, Allen teaches the coating wherein the dissolvable matrix is alginate hydrogel (paragraph 0084).
Regarding claims 5-6, Allen teaches the coating wherein the dissolvable matrix is dissolvable by a chelating agent, enzyme, or combination thereof, wherein the chelating agent is EDTA, EGTA, or sodium citrate. (paragraph 0084).
Regarding claim 8, Allen teaches the coating wherein the plurality of cell capture molecules comprises an antibody or aptamer (paragraph 0126).
Regarding claim 9, Allen teaches the coating wherein the first cell surface feature comprises CD44 (paragraph 0112).
Regarding claim 10, Allen teaches the coating wherein the second cell surface feature comprises CD44, CD47, MET, EpCAM, CD34, CD38, CD19, CD105, CD133, ESA, CD24, ALDH, ALDH1, CD166, SP, CD20, CD 117, A201, EGFR, HER2, ERCC1, CXCR4, E-Cadherin, Mucin-1, Cytokeratin, PSA, PSMA, RRM1, Androgen Receptor, Estrogen Receptor, progesterone Receptor, IGF 1, EML4, Leukocyte Associated Receptor (LAR), or any combination thereof (paragraph 0112).
Regarding claim 11, Allen in view of Miyake teaches a method of isolating rare cells comprising: a. contacting the biomimetic coating of claim 1 (see rejection of claim 1 above) with a sample containing rare cells; b. capturing a rare cell on the biomimetic coating; and c. detecting the rare cell bound by a cell capture molecule; wherein a viability of the rare cells is maintained (see paragraphs 0010, 0085 and 0094). While Allen teaches that the sample can be infused into the device at a suitable linear flow rate of e.g. 27.5 microliter/min (paragraph 0125), the reference does not explicitly teach a sample flow velocity less than 20mm/s along a coated path length.
However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 11 are for any particular purpose or solve any stated problem, and the prior art teaches that sample flow rate may be varied based on the desired sample type to be analyzed (paragraph 0125). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the cell surface assay art.
Regarding claim 12, Allen teaches the method wherein the chip provided with the coated capture zones (coated path) can have an overall chip length of 75mm, but the reference does not specifically teach that the coated pathlength is greater than 20mm.
However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 12 are for any particular purpose or solve any stated problem, and the prior art teaches that channel dimensions can be determined in order to manipulate flow shear forces (paragraph 0148). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the microfluidic assay art.
Regarding claim 13, while Allen teaches that the viability of the rare cells is maintained (paragraph 0085 and for example, claim 82), the reference does not specifically teach the method wherein the rare cells are maintained at 4°C to maintain viability. However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 13 are for any particular purpose or solve any stated problem, and the prior art teaches that it is of utmost important to maintain viability of the rare cell, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the cell isolation art.
Regarding claim 14, Allen teaches the method wherein the sample is selected from the group comprising whole blood, blood fractions such as serum and plasma, urine, sweat, lymph, feces, ascites, seminal fluid, sputum, nipple aspirate, post-operative seroma, wound drainage fluid, saliva, synovial fluid, ascites fluid, bone marrow aspirate, cerebrospinal fluid, nasal secretions, amniotic fluid, bronchoalveolar lavage fluid, pleural effusion, peripheral blood mononuclear cells, total white blood cells, lymph node cells, spleen cells, and tonsil cells (paragraph 0072).
Regarding claim 15, Allen teaches the method wherein the sample is treated with an anti-clotting agent (paragraph 0102).
Regarding claim 16, Allen teaches the method wherein detecting comprises microscopy or flow cytometry (paragraph 0111).
Regarding claim 17, Allen teaches the method further comprising contacting the biomimetic coating, comprising a captured rare cell, with media to maintain the viability of the captured rare cell (paragraph 0091).
Regarding claim 18, Allen teaches the method further comprising analyzing the isolated cells, wherein analysis comprises one or more of image analysis, cell number analysis, cell morphology analysis, polymerase chain reaction (PCR) analysis, sequence analysis, DNA analysis, RNA analysis, gene expression profiling, proteome analysis, metabolome analysis, immunoassays, RNA analysis, gene expression profiling, epigenetic analysis, proteome analysis, metabolome analysis, immunoassays, and nuclear exclusion analysis (paragraph 0113).
Regarding claim 35, Allen in view of Miyake teaches a method of determining a targeted therapy in a subject diagnosed with cancer comprising: a. contacting the biomimetic coating of claim 1 (see rejection of claim 1 above) with a sample containing rare cells b. capturing a rare cell on the biomimetic coating wherein a viability of the rare cell is maintained; c. detecting the rare cell bound by a cell capture molecule; d. removing the rare cell from the biomimetic coating; e. performing genome sequencing of the rare cell; f. determining a mutation in the cells; and g. determining a target therapeutic regime to target the mutation (see paragraphs 0010, 0015, 0084-0085 and 0094).
While Allen teaches that the sample can be infused into the device at a suitable linear flow rate of e.g. 27.5 microliter/min (paragraph 0125), the reference does not explicitly teach a sample flow velocity less than 20mm/s along a coated path length.
However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 35 are for any particular purpose or solve any stated problem, and the prior art teaches that sample flow rate may be varied based on the desired sample type to be analyzed (paragraph 0125). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the cell surface assay art.
Regarding claim 36, Allen teaches the method further comprising administering one or more chemotherapeutic agents to the subject (paragraph 0015).
Regarding claim 37, Allen teaches the method wherein the sample is selected from the group comprising whole blood, blood fractions such as serum and plasma, urine, sweat, lymph, feces, ascites, seminal fluid, sputum, nipple aspirate, post-operative seroma, wound drainage fluid, saliva, synovial fluid, ascites fluid, bone marrow aspirate, cerebrospinal fluid, nasal secretions, amniotic fluid, bronchoalveolar lavage fluid, pleural effusion, peripheral blood mononuclear cells, total white blood cells, lymph node cells, spleen cells, and tonsil cells (paragraph 0072).
Regarding claim 38, Allen teaches the method wherein detecting comprises microscopy or flow cytometry (paragraph 0111).
Regarding claim 39, Allen teaches the method wherein the cancers may include, but are not limited to, the following organs or systems: brain, cardiac, lung, gastrointestinal, genitourinary tract, liver, bone, nervous system, gynecological, hematologic, skin, breast, and adrenal glands. Additional types of cancer cells include gliomas (Schwannoma, glioblastoma, astrocytoma), neuroblastoma, pheochromocytoma, paraganlioma, meningioma, adrenalcortical carcinoma, medulloblastoma, rhabdomyoscarcoma, kidney cancer, vascular cancer of various types, osteoblastic osteocarcinoma, prostate cancer, ovarian cancer, uterine leiomyomas, salivary gland cancer, choroid plexus carcinoma, mammary cancer, pancreatic cancer, colon cancer, and megakaryoblastic leukemia; and skin cancers including malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, sarcomas such as fibrosarcoma or hemangiosarcoma, and melanoma (paragraph 0116).
Regarding claim 40, Allen in view of Miyake teach the method for determining responsiveness of a subject to a therapeutic regime comprising: a) introducing a fluid sample obtained from the subject into a microfluidic device and causing a rare cell cluster, bulk tumor cell, or bulk tumor cell cluster of the fluid sample to traverse a capture zone, wherein the capture zone comprises: i. a nonporous substrate; ii. the biomimetic coating of claim 1 (see claim 1 rejection above); and iii. a detector for detecting the rare cells; and b) isolating and analyzing the rare cells, wherein analysis comprises comparing a parameter of the rare cells to a reference parameter, thereby determining the responsiveness of the subject to a therapeutic regime (see paragraphs 0014 and 0008).
Regarding claim 41, Allen teaches the method wherein the sample is selected from the group comprising whole blood, blood fractions such as serum and plasma, urine, sweat, lymph, feces, ascites, seminal fluid, sputum, nipple aspirate, post-operative seroma, wound drainage fluid, saliva, synovial fluid, ascites fluid, bone marrow aspirate, cerebrospinal fluid, nasal secretions, amniotic fluid, bronchoalveolar lavage fluid, pleural effusion, peripheral blood mononuclear cells, total white blood cells, lymph node cells, spleen cells, and tonsil cells (paragraph 0072).
Regarding claim 42, Allen teaches the method wherein the sample is treated with an anti-clotting agent (paragraph 0102).
Regarding claim 43, Allen teaches the method wherein analyzing comprises one or more of image analysis, cell number analysis, cell morphology analysis, polymerase chain reaction (PCR) analysis, sequence analysis, DNA analysis, RNA analysis, gene expression profiling, epigenetic analysis, proteome analysis, metabolome analysis, immunoassays, and nuclear exclusion analysis (paragraph 0113).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. EP3444034 teaches a flow channel coated with molecule directed to surface structures of target cells (paragraph 0012) wherein the capture surface is coated with hydrogels (paragraph 0023) for enhanced immobilization capacity for biomolecules capable of binding the target cells (paragraph 0026).
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677