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
Claims 1-22 are pending
Claims 1-22 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-22 have an effective filing date of 05/11/2018, corresponding to PRO 62/670,528 and PRO 62/670,516.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/03/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly the information disclosure statement is being considered by the examiner.
Claim Rejections
35 U.S.C. 102(a)(1)
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, 2, 4-7, 9, 10, 12-14, 17-19, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Perritt et al. (US PG PUB 2016/0339165, publication date: 11/24/2016).
Perritt et al. disclose “[m]ethods (300), devices, and systems of processing blood are described. The method (300) comprises the steps of: obtaining (312) blood from a patient coupled to a single blood processing device to form a closed loop between the patient and the blood processing device; collecting (314) bulk mononuclear blood cells from the blood by leukapheresis implemented using the blood processing device in the closed loop; and enriching (316) concurrently target cells separated from non-target cells in the bulk mononuclear blood cells using the blood processing device in the closed loop.” See Abstract.
At [0019], Perritt et al. disclose that “[i]n accordance with an aspect of the invention, there is provided an apparatus for processing blood. The apparatus comprises: an inlet interface for coupling with a patient to receive blood directly from the circulation of the patient; a leukapheresis module [cell separation module] coupled to the inlet interface for collecting bulk mononuclear blood cells from the received blood; an enrichment module coupled to the leukapheresis module for enriching concurrently target cells separated from non-target cells in the bulk mononuclear blood cells; an outlet interface coupled to at least one of the leukapheresis module and the enrichment module for coupling with the patient to return enriched target cells to the circulation of the patient, the apparatus and the patient forming a closed loop when coupled together; and a controller for automated control of operation of the inlet and outlet interfaces, the leukapheresis module, and the enrichment module.” At [0009], Perritt et al. disclose the apparatus for processing blood may comprise a modification module [cell customization module] - “[C]ell manipulation (modification) devices, 140, can be employed in this scheme and include, but are not limited to: electroporation, lipofection, viral transduction, light (UVA, UVB, etc.), addition of drugs, cell activation, pressure, heating functions, etc.”
Based upon [0125] of Perritt et al., it appears that the leukapheresis module [cell separation module] includes a sampling step for cell counting and flow cytometry, and the enrichment module also includes a sampling step for cell counting and flow cytometry, see [0134].
At [0088], Perritt et al. disclose that “[m]odification may also be performed as a discontinuous ex vivo cell modification to alter cell phenotype, genotype or activity. This can be by the addition of cytokines, cross linking specific receptors, addition of antigen, transfection of DNA, RNA or protein, apoptotic cell induction, gene incorporation including viral transduction. In this embodiment, the enriched target cell population 1160 is withdrawn for a separate discontinuous modification step to alter cell phenotype/genotype/activity. The modified cells can then be used for research or for therapeutic application by infusing back into a patient. The degree of enrichment is that required for research/testing purposes or for the therapeutic application.”
At [0098], Perritt et al. disclose that “[i]n a further embodiment, the embodiments of the invention allow for monitoring the steps as the steps occur, that is, in real time such as the measurement of hematocrit, cell number, cell phenotype, cell activation, cell size, etc.” Also at [0062], Perritt et al. disclose various sensors, including collect pressure sensors and bowl pressure sensors, that detect various parameters in the blood processing device, and at [000246] of the specification, it is stated that detector modules monitor and detect various parameters. As such the invention of Parrett et al. meets the limitations of a detector configured to conduct a detection operation and operably interfaced with the cell separation module and/or the cell customization module.
At [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device. At [0009], Perritt et al. disclose that the blood processing device removes blood from the patient, processes, and returns the blood, and absent evidence to the contrary, this process involves parenteral, presumably, intravenous, communication with a patient.
At [0037], Perritt et al. disclose that “[t]he flow of blood from the patient to the device and back to the patient in which non-target cells generally return to the patient whereas target cells may be collected, may flow past an enrichment system in the device, may be modified by a modification system in the device and then return to the patient; all in a closed-loop patient-connected manner and in real time.”
At [0008], Perritt et al. teach that “[i]n addition to the enrichment process described above, the PBPC collected may also be modified in further processes before re-infusing back to the individual. This is generally effected by the use of a variety of techniques in cell culture. Ultimately, the modified cells (for example, altered phenotype, genotype or activity) may be re-introduced into the patient for certain therapeutic benefits.” Therefore it appears that the methods of Perritt et al. may or may not include cell culture steps in addition to the enrichment process.
As such Perritt et al. disclose a method of introducing a modification to a target nucleated blood cell, the method comprising:
parenterally connecting a subject in need of such modification to a system via the inlet and outlet conduits, the system comprising:
an inlet conduit adapted for parenteral communication with the subject and adapted for receiving blood from the subject;
a cell separation module in fluid communication with the inlet conduit, the cell separation module comprising a cell separator configured to produce a fraction enriched in a target nucleated blood cell type using the blood from the subject, and the cell separation module,
a cell customization module in fluid communication with the cell separation module so as to receive the nucleated blood cell fraction enriched in the target cell type from the cell separation module, the cell customization module configured to present one or more modifying agents to the target nucleated blood cells, wherein the cell customization module comprises a conduit that permits the target nucleated blood cells exposed to the one or more modifying age to pass out of the cell customization module, and
an outlet conduit in fluid communication with the cell separation module or the conduit of the cell customization module and adapted for parenteral communication with the subject, and the inlet conduit, the cell separation module, the cell customization module, and the outlet conduit of the system are connected in a fluid-sealed closed-loop;
permitting the blood of the subject to flow into the cell separation module and producing a fraction enriched in a target nucleated blood cell type;
permitting a blood cell fraction enriched in the target cell type to flow from the cell separation module to the cell customization module and contacting the blood cell fraction enriched in the target cell type with one or more modifying agents; and
permitting the target nucleated blood cells exposed to the one or more modifying agent to parenterally flow to the subject via the outlet conduit,
wherein the target nucleated blood cell type is not cultured or otherwise expanded in population prior to the target nucleated blood cells exposed to the one or more modifying agent to parenterally flowing to the subject via the outlet conduit, thus meeting the limitations of claim 1.
With respect to claim 2, at [0037], Perritt et al. teach that the methods of the invention involve continuous flow - “ [the] flow of blood from the patient to the device and back to the patient in which non-target cells generally return to the patient whereas target cells may be collected, may flow past an enrichment system in the device, may be modified by a modification system in the device and then return to the patient; all in a closed-loop patient-connected manner and in real time.”
With respect to claim 4, at [0036], Perritt et al. teach that “[m]ethods, apparatuses, and systems for processing blood cells are described hereinafter. In particular, methods, apparatuses, and systems are disclosed for leukapheresis that enable the concurrent collection and enrichment of specific target cells from an individual’s peripheral blood and the remaining blood components are returned to the individual. Additionally, the target cells collected may be modified and returned to the individual during the apheresis process, or may be returned to the individual at a later time…” These method steps would require some sort of means or kit that introduces a modifying agent to cells from a patient.
With respect to claim 5, as indicated above, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device, and said processor would be operably linked with either the device detector, cell separation module, and/or cell customization module in order to control device operation.
With respect to claims 6 and 7, at [0048], Perritt et al. disclose that “[t]he modifying step 320 may involve modification that is effected by at least one of cross linking cell surface receptors, irradiation, and treatment with at least one of cytokines, chemokines, antigen stimulation, hormones, drugs, pressure, and heating. The irradiation may be at least one of gamma, beta, alpha, and light radiation. The light radiation may be at least one of ultraviolet A (UVA), ultraviolet B (UVB), and visible light. Alternatively, the modifying step 320 may involve genetic modification that is effected by one of transfection and transduction of genetic material into at least a portion of the target cells. Transfection of genetic material may be by one of electroporation and lipofection.” Therefore Perritt et al. at least disclose modifying agents that are cytokines or nucleic acids.
With respect to claim 9, at [0068], Perritt et al. disclose that the biological delivery system may be used to treat patients having leukemic cells or metastatic cancer cells.
With respect to claims 10 and 21, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device.
With respect to claims 12 and 13, at [0062], Perritt et al. disclose various sensors, including collect pressure sensors and bowl pressure sensors, that detect various parameters in the blood processing device, and at [000246] of the specification, it is stated that detector modules monitor and detect various parameters. As such the invention of Parrett et al. meets the limitations of a detector configured to conduct a detection operation.
With respect to claim 14, based upon [0125] of Perritt et al., it appears that the leukapheresis module [cell separation module] includes a sampling step for cell counting and flow cytometry, and the enrichment module also includes a sampling step for cell counting and flow cytometry, see [0134].
With respect to claims 17-19, Perritt et al. disclose methods of using a reagent that specifically binds a desired cell-surface marker, thereby enriching for a desired subset of cells, and Perritt et al. disclose that selection methods may be based on cell acoustics - “In step 316, target cells separated from non-target cells in the bulk mononuclear blood cells are enriched concurrently using the blood-processing device in the closed loop. The target cells may be B cells, T cells, dendritic cells, monocytes, neutrophils, natural killer (NK) cells, T regulatory cells, T helper cells, cytotoxic T lymphocytes (CTLs), hematopoietic stem cells (HSCs), hematopoietic progenitor cells, endothelial cells, epithelial cells, mesenchymal cells, lymphocytes, lymphokine activated killer cells (LAKs), or tumor infiltrating lymphocytes (TILs). The T cells may be enriched. The T cells may be CD8+ or CD4+. The hematopoietic progenitor cells and the hematopoietic stem cells may be enriched. The hematopoietic stem cells and the hematopoietic progenitor cells may be positive for one or more of CD34, CD133, and CD143. Alternatively, the target cells may be at least one of malignant cells from blood, malignant cells from tissue, virally infected cells, bacterially infected cells, at least one virus, at least one bacterium, a parasite, fetal cells, and pathogenic effector cells… The enriching step 316 may comprise ligand capture to enrich the target cells. The ligand may be an antibody specific for a cell surface ligand. The cell surface ligand may be an epithelial cell adhesion molecule (EpCAM), a selectin, an adhesion molecule receptor, a homing receptor, a cytokine receptor, a chemokine receptor, or an enzyme. The cell surface ligand may be a cluster designation (CD) antigen. The CD antigen may be CD1a, CD4, CD8, CD14, CD25, CD34, CD133, or CD143. The target cell enrichment in step 316 may be effected by at least one of magnetics, fluorescent activated cell sorting, microfluidics, solid support, acoustics, bioluminescence, antibody tagging, and enzyme substrate. The solid support may comprise a particle. The particle may be at least one of a magnetic particle and a density modified particle (emphasis added).” See [0045]-[0046].
Therefore all of the limitations of claims 1, 2, 4-7, 9, 10, 12-14, 17-19, and 21 are met by Perritt et al.
35 U.S.C. 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.
Claims 3, 8, 11, 15, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Perritt et al. (US PG PUB 2016/0339165, publication date: 11/24/2016), as applied to claims 1, 2, 4-7, 9, 10, 12-14, 17-19, and 21, and further in view of Bosch et al. (US PG PUB 2005/0173315, publication date 08/11/2015).
As indicated above Perritt et al. disclose a method of introducing a modification to a target nucleated blood cell, the method comprising:
parenterally connecting a subject in need of such modification to a system via the inlet and outlet conduits, the system comprising:
an inlet conduit adapted for parenteral communication with the subject and adapted for receiving blood from the subject;
a cell separation module in fluid communication with the inlet conduit, the cell separation module comprising a cell separator configured to produce a fraction enriched in a target nucleated blood cell type using the blood from the subject, and the cell separation module,
a cell customization module in fluid communication with the cell separation module so as to receive the nucleated blood cell fraction enriched in the target cell type from the cell separation module, the cell customization module configured to present one or more modifying agents to the target nucleated blood cells, wherein the cell customization module comprises a conduit that permits the target nucleated blood cells exposed to the one or more modifying age to pass out of the cell customization module, and
an outlet conduit in fluid communication with the cell separation module or the conduit of the cell customization module and adapted for parenteral communication with the subject, and the inlet conduit, the cell separation module, the cell customization module, and the outlet conduit of the system are connected in a fluid-sealed closed-loop;
permitting the blood of the subject to flow into the cell separation module and producing a fraction enriched in a target nucleated blood cell type;
permitting a blood cell fraction enriched in the target cell type to flow from the cell separation module to the cell customization module and contacting the blood cell fraction enriched in the target cell type with one or more modifying agents; and
permitting the target nucleated blood cells exposed to the one or more modifying agent to parenterally flow to the subject via the outlet conduit,
wherein the target nucleated blood cell type is not cultured or otherwise expanded in population prior to the target nucleated blood cells exposed to the one or more modifying agent to parenterally flowing to the subject via the outlet conduit.
Perritt et al. do not teach or suggest a subject-connected, closed-loop system for the modification of a cell, the system comprising: a temperature control unit that maintains a temperature of approx. 37°C and a cell-washing unit that mixes target cells with a wash solution that dilutes a plasma component from the target cells. These deficiencies are remedied by Bosch et al.
Bosch et al. teach a bioreactor for preparing enriched leukocyte populations, see [0013], and at [0074], Bosch et al. teach that “[i]n another exemplary embodiment, an enriched population of leukocytes can be transferred to a bioreactor. The bioreactor can be equipped with appropriate inlets and/or outlets for introducing cells, sterile gas (e.g., oxygen, carbon dioxide, and/or air), tissue culture media, and the like. The bioreactor can also have means for controlling the temperature. The bioreactor is typically operated at about 37°C.” At [0016], Bosch et al. teach that the device comprises a wash inlet that allows for the introduction of fluids to wash recovered cells.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Perritt et al. and Bosch et al. to develop a method of introducing a modification to a target nucleated blood cell, the method comprising:
parenterally connecting a subject in need of such modification to a system via the inlet and outlet conduits, the system comprising:
an inlet conduit adapted for parenteral communication with the subject and adapted for receiving blood from the subject;
a cell separation module in fluid communication with the inlet conduit, the cell separation module comprising a cell separator configured to produce a fraction enriched in a target nucleated blood cell type using the blood from the subject, and the cell separation module,
a cell customization module in fluid communication with the cell separation module so as to receive the nucleated blood cell fraction enriched in the target cell type from the cell separation module, the cell customization module configured to present one or more modifying agents to the target nucleated blood cells, wherein the cell customization module comprises a conduit that permits the target nucleated blood cells exposed to the one or more modifying age to pass out of the cell customization module, and
an outlet conduit in fluid communication with the cell separation module or the conduit of the cell customization module and adapted for parenteral communication with the subject, and the inlet conduit, the cell separation module, the cell customization module, and the outlet conduit of the system are connected in a fluid-sealed closed-loop;
permitting the blood of the subject to flow into the cell separation module and producing a fraction enriched in a target nucleated blood cell type;
permitting a blood cell fraction enriched in the target cell type to flow from the cell separation module to the cell customization module and contacting the blood cell fraction enriched in the target cell type with one or more modifying agents; and
permitting the target nucleated blood cells exposed to the one or more modifying agent to parenterally flow to the subject via the outlet conduit,
wherein the target nucleated blood cell type is not cultured or otherwise expanded in population prior to the target nucleated blood cells exposed to the one or more modifying agent to parenterally flowing to the subject via the outlet conduit, and wherein a temperature control unit capable of reaching and maintaining temperatures within the unit of between 0°C and 37°C, inclusive; a cell washing unit comprising a chamber that mixes target nucleated blood cells with at least one wash solution that dilutes or removes a plasma component from the target nucleated blood cells and places washed cells into suspension prior to exposure to the one or more modifying agents; an inlet for introducing the one or more modifying agent to the suspension of washed cells, or a chamber comprising the one or more modifying agent into which a washed cell suspension is introduced. One of ordinary skill in the art would have been motivated to do so, because Perritt et al. disclose a method of introducing a modification to a target nucleated blood cell, the method comprising:
parenterally connecting a subject in need of such modification to a system via the inlet and outlet conduits, the system comprising:
an inlet conduit adapted for parenteral communication with the subject and adapted for receiving blood from the subject;
a cell separation module in fluid communication with the inlet conduit, the cell separation module comprising a cell separator configured to produce a fraction enriched in a target nucleated blood cell type using the blood from the subject, and the cell separation module,
a cell customization module in fluid communication with the cell separation module so as to receive the nucleated blood cell fraction enriched in the target cell type from the cell separation module, the cell customization module configured to present one or more modifying agents to the target nucleated blood cells, wherein the cell customization module comprises a conduit that permits the target nucleated blood cells exposed to the one or more modifying age to pass out of the cell customization module, and
an outlet conduit in fluid communication with the cell separation module or the conduit of the cell customization module and adapted for parenteral communication with the subject, and the inlet conduit, the cell separation module, the cell customization module, and the outlet conduit of the system are connected in a fluid-sealed closed-loop;
permitting the blood of the subject to flow into the cell separation module and producing a fraction enriched in a target nucleated blood cell type;
permitting a blood cell fraction enriched in the target cell type to flow from the cell separation module to the cell customization module and contacting the blood cell fraction enriched in the target cell type with one or more modifying agents; and
permitting the target nucleated blood cells exposed to the one or more modifying agent to parenterally flow to the subject via the outlet conduit,
wherein the target nucleated blood cell type is not cultured or otherwise expanded in population prior to the target nucleated blood cells exposed to the one or more modifying agent to parenterally flowing to the subject via the outlet conduit. Furthermore Bosch et al. teach that bioreactors for use in cell manipulation may be maintained at about 37°C and may also include fluids to wash recovered cells, which would be expected to dilute a plasma component from target cell populations. One of ordinary skill in the art would have been motivated to modify the invention of Perritt et al. to comprise the elements of Bosch et al., because such a modification would provide a means of maintaining cell populations at an appropriate temperature and washing cells to remove/dilute contaminants. The invention of Perritt et al. and Bosch et al. meets the limitations of claim 11.
With respect to claim 3, in view of the teachings of Perritt et al., one of ordinary skill in the art would have been motivated to include multiple holding units for processing cells with different modifying agents. According to [0077] of Perritt et al., “[d]uring the enrichment step, more than one target cell type may be enriched. The system may enrich multiple cell types in various ways, eg the cell types may be enriched separately in different chambers of the device... The different cell types may be managed together (eg all returned or discarded or modified) or the cell types may be managed separately (eg one set returned, one set discarded, one set modified or all sets modified but in different ways)…”
With respect to claims 15 and 16, at [0125], Perritt et al. teaches that target cells may be enriched and counted. As such one of ordinary skill in the art would have been motivated to count target cells in order to determine when a desired number (or threshold) of cells has been obtained. Furthermore at [0103], Perritt et al. teach that “[t]he Therakos CellEx Photopheresis System formed the basis of the blood-processing device. As depicted in FIG. 9, the system 900 comprises several components including a centrifuge chamber 962, a pump deck 964, a photoactivation chamber, and a user-friendly software driven operator interface 960. Additional clamps and pumps are added as required and a CellEx Photopheresis procedure specific single-use disposable set was modified for use in this example. In the present example of collection of mononuclear cells and enrichment of CD4+ cells from peripheral blood, the photoactivation chamber is not required. The CellEx Photopheresis System uses a one-omega two-omega centrifugation technology that, in combination with a Latham bowl coupled to a three-port lumen drive tube, allows for continuous whole blood processing. Compared to other leukapheresis devices, collection of a similar number of mononuclear cells can be achieved from a reduced extracorporeal volume. The CellEx Photopheresis System can be operated in single (batch return) or double needle (continuous return) mode of access, which provides flexibility for the patient. In the present example, double needle mode was employed for single pass of blood from the faux patient bag to the faux patient return bag (emphasis added).”
With respect to claim 20, one of ordinary skill in the art would appreciate that the invention of Perritt et al. and Bosch et al. could be used in hospital settings, including bedside settings, to treat cancer patients, including leukemia patients, and as such the system of Perritt et al. and Bosch et al. may be used as a bedside system adapted for treating a condition involving blood cells (leukemia).
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Nonstatutory 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.
Claims 1-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,904,081.
Although the claims at issue are not identical, they are not patentably distinct from each other, because sets of claims recite similar systems for cell modification, including methods of introducing a modification to a target nucleated blood cell. The systems of the instant and conflicting claims recite similar cell separation modules, cell customization modules, and inlet/outlet conduits. Both claim sets also encompass similar modifying agents (such as one or more nucleic acids encoding a chimeric antigen receptor (CAR)), system processors, temperature control units, detectors, sampling units, apheresis modules, and purification units.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over a) claim 1 of U.S. Patent No. 10,926,020, b) claim 1 of U.S. Patent No. 10,940,259, c) claim 1 of U.S. Patent No. 10,953,109, and d) claim 1 of U.S. Patent No. 12,447,253, in view of Perritt et al. (US PG PUB 2016/0339165, publication date: 11/24/2016), and Bosch et al. (US PG PUB 2005/0173315, publication date 08/11/2015).
The teachings of Perritt et al. and Bosch et al. are detailed above.
Conflicting claim 1 does not recite a system that comprises a cell customization module or inlet/outlet conduits.
The teachings of Perritt et al. and Bosch et al. are detailed above.
Based upon the teachings of Perritt et al., it would have been obvious to modify conflicting claim 1 to comprise a cell customization module and inlet/outlet conduits, because the resultant device could be used in the treatment of biological delivery system may be used to treat patients having leukemic cells or metastatic cancer cells.
With respect to claim 2, at [0037], Perritt et al. teach that the methods of the invention involve continuous flow - “ [the] flow of blood from the patient to the device and back to the patient in which non-target cells generally return to the patient whereas target cells may be collected, may flow past an enrichment system in the device, may be modified by a modification system in the device and then return to the patient; all in a closed-loop patient-connected manner and in real time.”
With respect to claim 4, at [0036], Perritt et al. teach that “[m]ethods, apparatuses, and systems for processing blood cells are described hereinafter. In particular, methods, apparatuses, and systems are disclosed for leukapheresis that enable the concurrent collection and enrichment of specific target cells from an individual’s peripheral blood and the remaining blood components are returned to the individual. Additionally, the target cells collected may be modified and returned to the individual during the apheresis process, or may be returned to the individual at a later time…” These method steps would require some sort of means or kit that introduces a modifying agent to cells from a patient.
With respect to claim 5, as indicated above, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device, and said processor would be operably linked with either the device detector, cell separation module, and/or cell customization module in order to control device operation.
With respect to claims 6 and 7, at [0048], Perritt et al. disclose that “[t]he modifying step 320 may involve modification that is effected by at least one of cross linking cell surface receptors, irradiation, and treatment with at least one of cytokines, chemokines, antigen stimulation, hormones, drugs, pressure, and heating. The irradiation may be at least one of gamma, beta, alpha, and light radiation. The light radiation may be at least one of ultraviolet A (UVA), ultraviolet B (UVB), and visible light. Alternatively, the modifying step 320 may involve genetic modification that is effected by one of transfection and transduction of genetic material into at least a portion of the target cells. Transfection of genetic material may be by one of electroporation and lipofection.” Therefore Perritt et al. at least disclose modifying agents that are cytokines or nucleic acids.
With respect to claim 9, at [0068], Perritt et al. disclose that the biological delivery system may be used to treat patients having leukemic cells or metastatic cancer cells.
With respect to claims 10 and 21, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device.
With respect to claims 12 and 13, at [0062], Perritt et al. disclose various sensors, including collect pressure sensors and bowl pressure sensors, that detect various parameters in the blood processing device, and at [000246] of the specification, it is stated that detector modules monitor and detect various parameters. As such the invention of Parrett et al. meets the limitations of a detector configured to conduct a detection operation.
With respect to claim 14, based upon [0125] of Perritt et al., it appears that the leukapheresis module [cell separation module] includes a sampling step for cell counting and flow cytometry, and the enrichment module also includes a sampling step for cell counting and flow cytometry, see [0134].
With respect to claim 11, one of ordinary skill in the art would have been motivated to modify the invention of the conflicting claims and Perritt et al. to comprise the elements of Bosch et al., because such a modification would provide a means of maintaining cell populations at an appropriate temperature and washing cells to remove/dilute contaminants.
With respect to claim 3, in view of the teachings of Perritt et al., one of ordinary skill in the art would have been motivated to include multiple holding units for processing cells with different modifying agents. According to [0077] of Perritt et al., “[d]uring the enrichment step, more than one target cell type may be enriched. The system may enrich multiple cell types in various ways, eg the cell types may be enriched separately in different chambers of the device... The different cell types may be managed together (eg all returned or discarded or modified) or the cell types may be managed separately (eg one set returned, one set discarded, one set modified or all sets modified but in different ways)…”
With respect to claims 15 and 16, at [0125], Perritt et al. teaches that target cells may be enriched and counted. As such one of ordinary skill in the art would have been motivated to count target cells in order to determine when a desired number (or threshold) of cells has been obtained. Furthermore at [0103], Perritt et al. teach that “[t]he Therakos CellEx Photopheresis System formed the basis of the blood-processing device. As depicted in FIG. 9, the system 900 comprises several components including a centrifuge chamber 962, a pump deck 964, a photoactivation chamber, and a user-friendly software driven operator interface 960. Additional clamps and pumps are added as required and a CellEx Photopheresis procedure specific single-use disposable set was modified for use in this example. In the present example of collection of mononuclear cells and enrichment of CD4+ cells from peripheral blood, the photoactivation chamber is not required. The CellEx Photopheresis System uses a one-omega two-omega centrifugation technology that, in combination with a Latham bowl coupled to a three-port lumen drive tube, allows for continuous whole blood processing. Compared to other leukapheresis devices, collection of a similar number of mononuclear cells can be achieved from a reduced extracorporeal volume. The CellEx Photopheresis System can be operated in single (batch return) or double needle (continuous return) mode of access, which provides flexibility for the patient. In the present example, double needle mode was employed for single pass of blood from the faux patient bag to the faux patient return bag (emphasis added).”
With respect to claims 17-19, Perritt et al. disclose methods of using a reagent that specifically binds a desired cell-surface marker, thereby enriching for a desired subset of cells, and Perritt et al. disclose that selection methods may be based on cell acoustics - “In step 316, target cells separated from non-target cells in the bulk mononuclear blood cells are enriched concurrently using the blood-processing device in the closed loop. The target cells may be B cells, T cells, dendritic cells, monocytes, neutrophils, natural killer (NK) cells, T regulatory cells, T helper cells, cytotoxic T lymphocytes (CTLs), hematopoietic stem cells (HSCs), hematopoietic progenitor cells, endothelial cells, epithelial cells, mesenchymal cells, lymphocytes, lymphokine activated killer cells (LAKs), or tumor infiltrating lymphocytes (TILs). The T cells may be enriched. The T cells may be CD8+ or CD4+. The hematopoietic progenitor cells and the hematopoietic stem cells may be enriched. The hematopoietic stem cells and the hematopoietic progenitor cells may be positive for one or more of CD34, CD133, and CD143. Alternatively, the target cells may be at least one of malignant cells from blood, malignant cells from tissue, virally infected cells, bacterially infected cells, at least one virus, at least one bacterium, a parasite, fetal cells, and pathogenic effector cells… The enriching step 316 may comprise ligand capture to enrich the target cells. The ligand may be an antibody specific for a cell surface ligand. The cell surface ligand may be an epithelial cell adhesion molecule (EpCAM), a selectin, an adhesion molecule receptor, a homing receptor, a cytokine receptor, a chemokine receptor, or an enzyme. The cell surface ligand may be a cluster designation (CD) antigen. The CD antigen may be CD1a, CD4, CD8, CD14, CD25, CD34, CD133, or CD143. The target cell enrichment in step 316 may be effected by at least one of magnetics, fluorescent activated cell sorting, microfluidics, solid support, acoustics, bioluminescence, antibody tagging, and enzyme substrate. The solid support may comprise a particle. The particle may be at least one of a magnetic particle and a density modified particle.” See [0045]-[0046].
With respect to claim 20, one of ordinary skill in the art would appreciate that the invention of Perritt et al. and Bosch et al. could be used in hospital settings, including bedside settings, to treat cancer patients, including leukemia patients, and as such the system of Perritt et al. and Bosch et al. may be used as a bedside system adapted for treating a condition involving blood cells (leukemia).
Therefore the instant claims are prima facie obvious over the conflicting claims in view of the references cited.
Claims 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/299,923 in view of view of Perritt et al. (US PG PUB 2016/0339165, publication date: 11/24/2016), and Bosch et al. (US PG PUB 2005/0173315, publication date 08/11/2015).
The teachings of Perritt et al. and Bosch et al. are detailed above.
Conflicting claim 1 does not recite a system that comprises a cell customization module or inlet/outlet conduits.
The teachings of Perritt et al. and Bosch et al. are detailed above.
Based upon the teachings of Perritt et al., it would have been obvious to modify conflicting claim 1 to comprise a cell customization module and inlet/outlet conduits, because the resultant device could be used in the treatment of biological delivery system may be used to treat patients having leukemic cells or metastatic cancer cells.
With respect to claim 2, at [0037], Perritt et al. teach that the methods of the invention involve continuous flow - “ [the] flow of blood from the patient to the device and back to the patient in which non-target cells generally return to the patient whereas target cells may be collected, may flow past an enrichment system in the device, may be modified by a modification system in the device and then return to the patient; all in a closed-loop patient-connected manner and in real time.”
With respect to claim 4, at [0036], Perritt et al. teach that “[m]ethods, apparatuses, and systems for processing blood cells are described hereinafter. In particular, methods, apparatuses, and systems are disclosed for leukapheresis that enable the concurrent collection and enrichment of specific target cells from an individual’s peripheral blood and the remaining blood components are returned to the individual. Additionally, the target cells collected may be modified and returned to the individual during the apheresis process, or may be returned to the individual at a later time…” These method steps would require some sort of means or kit that introduces a modifying agent to cells from a patient.
With respect to claim 5, as indicated above, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device, and said processor would be operably linked with either the device detector, cell separation module, and/or cell customization module in order to control device operation.
With respect to claims 6 and 7, at [0048], Perritt et al. disclose that “[t]he modifying step 320 may involve modification that is effected by at least one of cross linking cell surface receptors, irradiation, and treatment with at least one of cytokines, chemokines, antigen stimulation, hormones, drugs, pressure, and heating. The irradiation may be at least one of gamma, beta, alpha, and light radiation. The light radiation may be at least one of ultraviolet A (UVA), ultraviolet B (UVB), and visible light. Alternatively, the modifying step 320 may involve genetic modification that is effected by one of transfection and transduction of genetic material into at least a portion of the target cells. Transfection of genetic material may be by one of electroporation and lipofection.” Therefore Perritt et al. at least disclose modifying agents that are cytokines or nucleic acids.
With respect to claim 9, at [0068], Perritt et al. disclose that the biological delivery system may be used to treat patients having leukemic cells or metastatic cancer cells.
With respect to claims 10 and 21, at [0060], Perritt et al. disclose that the blood processing device comprises a processor that controls operations of the device.
With respect to claims 12 and 13, at [0062], Perritt et al. disclose various sensors, including collect pressure sensors and bowl pressure sensors, that detect various parameters in the blood processing device, and at [000246] of the specification, it is stated that detector modules monitor and detect various parameters. As such the invention of Parrett et al. meets the limitations of a detector configured to conduct a detection operation.
With respect to claim 14, based upon [0125] of Perritt et al., it appears that the leukapheresis module [cell separation module] includes a sampling step for cell counting and flow cytometry, and the enrichment module also includes a sampling step for cell counting and flow cytometry, see [0134].
With respect to claim 11, one of ordinary skill in the art would have been motivated to modify the invention of the conflicting claims and Perritt et al. to comprise the elements of Bosch et al., because such a modification would provide a means of maintaining cell populations at an appropriate temperature and washing cells to remove/dilute contaminants.
With respect to claim 3, in view of the teachings of Perritt et al., one of ordinary skill in the art would have been motivated to include multiple holding units for processing cells with different modifying agents. According to [0077] of Perritt et al., “[d]uring the enrichment step, more than one target cell type may be enriched. The system may enrich multiple cell types in various ways, eg the cell types may be enriched separately in different chambers of the device... The different cell types may be managed together (eg all returned or discarded or modified) or the cell types may be managed separately (eg one set returned, one set discarded, one set modified or all sets modified but in different ways)…”
With respect to claims 15 and 16, at [0125], Perritt et al. teaches that target cells may be enriched and counted. As such one of ordinary skill in the art would have been motivated to count target cells in order to determine when a desired number (or threshold) of cells has been obtained. Furthermore at [0103], Perritt et al. teach that “[t]he Therakos CellEx Photopheresis System formed the basis of the blood-processing device. As depicted in FIG. 9, the system 900 comprises several components including a centrifuge chamber 962, a pump deck 964, a photoactivation chamber, and a user-friendly software driven operator interface 960. Additional clamps and pumps are added as required and a CellEx Photopheresis procedure specific single-use disposable set was modified for use in this example. In the present example of collection of mononuclear cells and enrichment of CD4+ cells from peripheral blood, the photoactivation chamber is not required. The CellEx Photopheresis System uses a one-omega two-omega centrifugation technology that, in combination with a Latham bowl coupled to a three-port lumen drive tube, allows for continuous whole blood processing. Compared to other leukapheresis devices, collection of a similar number of mononuclear cells can be achieved from a reduced extracorporeal volume. The CellEx Photopheresis System can be operated in single (batch return) or double needle (continuous return) mode of access, which provides flexibility for the patient. In the present example, double needle mode was employed for single pass of blood from the faux patient bag to the faux patient return bag (emphasis added).”
With respect to claims 17-19, Perritt et al. disclose methods of using a reagent that specifically binds a desired cell-surface marker, thereby enriching for a desired subset of cells, and Perritt et al. disclose that selection methods may be based on cell acoustics - “In step 316, target cells separated from non-target cells in the bulk mononuclear blood cells are enriched concurrently using the blood-processing device in the closed loop. The target cells may be B cells, T cells, dendritic cells, monocytes, neutrophils, natural killer (NK) cells, T regulatory cells, T helper cells, cytotoxic T lymphocytes (CTLs), hematopoietic stem cells (HSCs), hematopoietic progenitor cells, endothelial cells, epithelial cells, mesenchymal cells, lymphocytes, lymphokine activated killer cells (LAKs), or tumor infiltrating lymphocytes (TILs). The T cells may be enriched. The T cells may be CD8+ or CD4+. The hematopoietic progenitor cells and the hematopoietic stem cells may be enriched. The hematopoietic stem cells and the hematopoietic progenitor cells may be positive for one or more of CD34, CD133, and CD143. Alternatively, the target cells may be at least one of malignant cells from blood, malignant cells from tissue, virally infected cells, bacterially infected cells, at least one virus, at least one bacterium, a parasite, fetal cells, and pathogenic effector cells… The enriching step 316 may comprise ligand capture to enrich the target cells. The ligand may be an antibody specific for a cell surface ligand. The cell surface ligand may be an epithelial cell adhesion molecule (EpCAM), a selectin, an adhesion molecule receptor, a homing receptor, a cytokine receptor, a chemokine receptor, or an enzyme. The cell surface ligand may be a cluster designation (CD) antigen. The CD antigen may be CD1a, CD4, CD8, CD14, CD25, CD34, CD133, or CD143. The target cell enrichment in step 316 may be effected by at least one of magnetics, fluorescent activated cell sorting, microfluidics, solid support, acoustics, bioluminescence, antibody tagging, and enzyme substrate. The solid support may comprise a particle. The particle may be at least one of a magnetic particle and a density modified particle.” See [0045]-[0046].
With respect to claim 20, one of ordinary skill in the art would appreciate that the invention of the conflicting claim, Perritt et al., and Bosch et al. could be used in hospital settings, including bedside settings, to treat cancer patients, including leukemia patients, and as such the system of Perritt et al. and Bosch et al. may be used as a bedside system adapted for treating a condition involving blood cells (leukemia).
Therefore the instant claims are prima facie obvious over the conflicting claims in view of the references cited.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights