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 .
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1- 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Teo (US 2020/0276586) in view of Liu (WO 2019233303).
Regarding claim 1, Teo teaches a microfluidic device comprising a cartridge housing (200); a central chamber (212) embedded in the cartridge housing; at least one aperture (216) fluidly connected to the central chamber (212); and a plurality of evenly spaced micropillars (208) arranged in a substantially circular shape within the central chamber (212) such that the central chamber is partitioned into at least a first inner region (206) and a first outer region (204).
Teo fails to teach wherein the first inner region comprises endothelial cells configured to mimic a venous sinus and the first outer region comprises endothelial cells and mesenchymal stromal cells configured to mimic a medullary cavity.
Liu teaches a microfluidic device with micropillars comprising circulating endothelial cells (blood samples) and mesenchymal stromal cells (bone marrow samples). Liu teaches “ (1) circulating tumor cells in peripheral blood samples; (2) tumor cells in pleural effusion, ascites fluid, lymph fluid, urine or bone marrow samples; (3) nucleated red blood cells in peripheral blood or umbilical cord blood samples; (4) circulating endothelial cells in peripheral blood samples; (5) Leukocytes, T cells, B cells, lymphocytes, monocytes, granulocytes, natural killer cells, dendrites in peripheral blood, umbilical cord blood, pleural effusion, ascites fluid, urine, cerebrospinal fluid or bone marrow samples Cells, macrophages or hematopoietic stem cells; (6) red blood cells or platelets in peripheral blood, umbilical cord blood, pleural effusion, ascites fluid, urine or bone marrow samples; (7) bacteria or viruses in peripheral blood, pleural effusion, ascites fluid, urine, saliva, plasma, serum, cerebrospinal fluid, semen, prostate fluid or vaginal secretion samples; (8) Isolate the sperm in the semen sample.”
It would have been obvious to one having ordinary skill in the art to provide the device of Teo with wherein the first inner region comprises endothelial cells configured to mimic a venous sinus and the first outer region comprises endothelial cells and mesenchymal stromal cells configured to mimic a medullary cavity as disclosed in Liu in order to analyze bone marrow and therefore increase the versatility of the device.
Regarding claim 2, the first inner region and the first outer region are concentric. Figure 2B, Teo)
Regarding claim 3, the central chamber (212) comprises an additional second outer region (fig. 2B, Teo) adjacent and concentric to the first outer region, the second outer region being defined by a plurality of evenly spaced micropillars (208) arranged in a substantially circular shape and comprising osteoblasts configured to mimic an endosteal region. (Figure 2B, Teo)
Regarding claim 4, the plurality of micropillars (208) have a cross- sectional shape selected from the group consisting of: circular, ovoid, square, rectangular, triangular, trapezoidal, and polygonal. (Figure 2B, Teo)
Regarding claim 5, the plurality of micropillars (208) are evenly spaced by a distance between about 50 µm and 200 µm. (Figure 2B, Teo)
Regarding claim 6, one or more sensors comprising capture molecules or probes positioned within the central chamber. Teo teaches “the lymphatic fluid subsequently travels through a number of smaller sinuses: the subcapsular sinus (SCS), the trabecular sinus, the medullary sinus through which it gets cleaned and finally leaves the lymph node at the hilus through the efferent lymphatic vessel. FRCs are situated close to the SCS where they can capture and transport antigens from the lymph fluid to the nearby-lying APCs. Particularly, the lymph nodes usually have one efferent vessel and multiple afferent ones. This allows the lymph node to act as a “settling tank” providing sufficient time for lymphocytes to recognize antigens and interact with APCs.”
Regarding claim 7, the capture molecule or probe is selected from the group consisting of: antibodies, antibody fragments, antigens, proteins, nucleic acids, oligonucleotides, peptides, lipids, lectins, inhibitors, activators, ligands, hormones, cytokines, sugars, amino acids, fatty acids, phenols, and alkaloids. ([0002 and [0064], Teo])
Regarding claim 8, the one or more sensors are positioned between each of the micropillars. ([0064, Teo])
Regarding claim 9, the one or more sensors are localized surface plasmon resonance nanoplasmonic biosensors. ([0005])
Regarding claim 10, the device is configured to replicate or mimic a bone marrow disease or disorder state selected from the group consisting of: leukemia, myeloma, anemia, infection, poisoning, and physical injury. (lymph nodes, Teo)
Regarding claim 11, a device replicating or mimicking a leukemia disease state comprises B-cell acute lymphoblastic leukemia (B-ALL) cells in the first outer region. ([0002, Teo])
Regarding claim 12, providing the device of claim 11; administering a leukemia treatment to the central chamber; and determining leukemia treatment responsiveness based on a measured change in the central chamber. ([0066, Teo])
Regarding claim 13, the leukemia treatment is a chemotherapeutic selected from the group consisting of: nilotinib, prednisone, vincristine, daunorubicin, doxorubicin, cytarabine, L-asparaginase, 6-mercaptopurine, methotrexate, cyclophosphamide, dexamethasone, and nelarabine. ([0098, Teo])
Regarding claim 14, the measured change is a quantity of live and dead B-ALL cells after 1-3 days treatment or more. ([0098, Teo])
Regarding claim 15, the leukemia treatment is chimeric antigen receptor (CAR) T-cell therapy, and wherein the central chamber further comprises CAR T-cells in the first inner region. ([0098, Teo])
Regarding claim 16, each of the cells in the central chamber are autologous cells. ([0002])
Regarding claim 17, the measured change is a percent of leukemia cells relative to total cell population in the central chamber that is 5% or less, indicating responsiveness to CAR T-cell therapy. ([0010])
Regarding claim 18, the measured change is a percent of leukemia cells relative to total cell population in the central chamber that is 25% or more, indicating non-responsiveness to CAR T-cell therapy. ([0002])
Regarding claim 19, the measured change is a decrease in CD19 expression in B-ALL cells, indicating non-responsiveness to CAR T-cell therapy. ([0002])
Regarding claim 20, the measured change is an increase in suppressor immune cells, indicating non-responsiveness to CAR T-cell therapy. ([0002])
Regarding claim 21, the measured change is an increase in cytokine levels selected from the group consisting of: IFN-γ, TNF-α, IL-2, and GZMB; indicating responsiveness to CAR T-cell therapy. ([0003])
Regarding claim 22, the measured change is an increase in cytokine levels selected from the group consisting of: TGF-ß, IL-10, M-CSF, and CCL2; indicating non-responsiveness to CAR T-cell therapy. ([0003])
Regarding claim 23, the measured change is an increase in surface markers selected from the group consisting of: CD154, CD69, and CD107a; indicating responsiveness to CAR T-cell therapy. ([0003])
Conclusion
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/JYOTI Mutreja/ Primary Examiner, Art Unit 1798
