Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Claims 1-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/24/25.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are:
a “controller to select a positive separation process or a negative separation process….”
in claim 8 and its dependent claim;
a “pipette pump to inject …” in claims 8, 9, 10, and 11, and their dependent claims;
a “magnetic separation rack to generate a magnetic field….” in claims 8, 9, 10, and 14;
an “oscillator to perform a mixing process…” in claims 9 and 10;
a “pressure sensor to detect a pressure change…” in claim 13.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The limitation of a “controller to select a positive separation process or a negative separation process….” is interpreted to encompass a controller generically disclosed by Applicant, such as in paragraph 0008 in the PreGrant Publication US 20230118289, and as generally understood by one skilled in the art, and its equivalent.
The limitation of a “pipette pump to inject …” is interpreted to encompass a pipette as generically disclosed by Applicant, such as in paragraph 0026, and as generally understood by one skilled in the art, and its equivalent.
The limitation of a “magnetic separation rack to generate a magnetic field….” is interpreted to encompass a magnetic separation rack as disclosed by Applicant, such as in paragraphs 0026, 0027, and 0031, and its equivalent.
The limitation of an “oscillator to perform a mixing process…” is interpreted to encompass an oscillator as disclosed by Applicant, such as in paragraphs 0028, 0033, 0045, 0047, 0053, 0056, and 0061, and its equivalent.
The limitation of a “pressure sensor to detect a pressure change…” is interpreted to encompass as pressure sensor as generally disclosed by Applicant, such as in paragraphs 0030, 0041, and 0042, and as generally understood by one skilled in the art, and its equivalent.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 8-12 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 20080057505 (hereinafter “Lin”).
Lin discloses Applicant’s claimed limitations as follows.
As to claim 8, Lin teaches a separating method of biosubstance, being used for processing a sample containing target biosubstances and non-target biosubstances,
the separating method comprising:
providing a controller to select a positive separation process or a negative separation process to execute according to types of the target biosubstances
[See para. 0185-0186 disclosing that the disclosed invention is performed by an automated instrument or system, and disclosure regarding an automated process].
[See para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)].
[See para. 0158 disclosing: ‘Frequently, the selective binding member is an antibody or antibody fragment that is selective for a cell surface marker that is associated with a non-target cell and is expected to be absent on the target cells. An example of such markers would be a surface antigen that occurs on one or more types of hematopoietic cells, when the target cell is a non-hematopoietic cell. The solid surface can be a surface of a container that the sample is placed in, or a surface of a swab or other item to be passed through the sample, or it can be a finely divided material such as a bead or gel that can be admixed with the sample. In each case, the sample is exposed to the solid surface for a sufficient period of time to permit binding of the non-target cell type to be removed to the specific binding member; then the sample is separated from the solid surface for further enrichment or analysis. In one preferred embodiment, the solid surface is a plurality of beads, such as magnetic beads, that provide a high surface area for affixing the specific binding member of interest, can be efficiently mixed with the sample to permit binding of the non-target cell to the specific binding material, and can be conveniently separated from the sample to remove the non-target cells.’ (emphasis added)].
[See para. 0164 disclosing: ‘the immuno-particles could be any solid phase particle or microspheres such as magnetic particle, sepharose, sephadex, and agarose etc based particles, and the particles can be chemically modified to conjugate to an antibody or any other specific binding members for selection and binding of non-target cell types to be removed as part of the process for enrichment of the sample in the target cell type of interest.’ (emphasis added)].
[See para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)].
Also regarding claim 8, Lin discloses providing a pipette pump to inject a first magnetic bead reagent or a second magnetic bead reagent into the sample according to the selected separation process, such that first immunomagnetic beads of the first magnetic bead reagent or second immunomagnetic beads of the second magnetic bead reagent binds to the target biosubstances
[See para. 0123 disclosing a sample to be pumped by a fluid through a conduit, or by means of a pipette, syringe, or other means of dispensing or transporting a sample].
[See para. 0145 disclosing: ‘"Continuous flow" means that fluid is pumped or injected into a chamber of the present invention continuously during the separation process. This allows for components of a sample that are not selectively retained in a chamber to be flushed out of the chamber during the separation process.’]
[See paras. 0029, 0037 disclosing that the microparticle may comprise a magnetic material to facilitate separation of the particle from the enriched sample].
[See paras. 0042 disclosing magnetic capture methods].
[See para. 0046 disclosing: “removing the remaining hematopoietic cells such as white blood cells (WBCs) by specific binding of said hematopoietic cells to specific binding members, such as binding WBCs to an anti-CD50 antibody or another leukocyte-specific antibody, which may be linked to a solid surface such as a microparticle or a magnetic particle, to enrich the sample with the targeted cancer cells, if any are present”].
[See para. 0048 disclosing, “Suitable means for removing WBCs are also disclosed herein, and include, for example microparticles that are optionally magnetic and are linked to at least one specific binding member that is selective for binding to leukocyte surface antigens.”]
[See para. 0089 disclosing: ‘"Binding partner" or "binding member" refers to any substances that both bind to the moieties with desired affinity or specificity and are manipulatable with the desired physical force(s). Non-limiting examples of the binding partners include cells, cellular organelles, viruses, microparticles or an aggregate or complex thereof, or an aggregate or complex of molecules.’]
[See para. 0090 disclosing: ‘"microparticle" or "particle" is a structure of any shape and of any composition that is manipulatable by desired physical force(s)… Examples of microparticles include, but are not limited to, plastic particles, ceramic particles, carbon particles, polystyrene microbeads, glass beads, magnetic beads, hollow glass spheres, metal particles, particles of complex compositions, microfabricated or micromachined particles, etc.’ (emphasis added)].
[See para. 0091 disclosing: ‘"Coupled" means bound. For example, a moiety can be coupled to a microparticle by specific or nonspecific binding. As disclosed herein, the binding can be covalent or noncovalent, reversible or irreversible.’ (emphasis added)].
[See para. 0092 disclosing: ‘As used herein, "the moiety to be manipulated is substantially coupled onto surface of the binding partner" means that a percentage of the moiety to be manipulated is coupled onto a surface of the binding partner and can be manipulated by a suitable physical force via manipulation of the binding partner…’ (emphasis added)].
[See para. 0128: disclosing: ‘"Separation" is a process in which one or more components of a sample are spatially separated from one or more other components of a sample. A separation can be performed such that one or more sample components of interest is translocated to or retained in one or more areas of a separation apparatus and at least some of the remaining components are translocated away from the area or areas where the one or more sample components of interest are translocated to and/or retained in, or in which one or more sample components is retained in one or more areas and at least some or the remaining components are removed from the area or areas. Alternatively, one or more components of a sample can be translocated to and/or retained in one or more areas and one or more sample components can be removed from the area or areas. It is also possible to cause one or more sample components to be translocated to one or more areas and one or more sample components of interest or one or more components of a sample to be translocated to one or more other areas. Separations can be achieved through, for example, filtration, or the use of physical, chemical, electrical, or magnetic forces. Nonlimiting examples of forces that can be used in separations are gravity, mass flow, dielectrophoretic forces, traveling-wave dielectrophoretic forces, and electromagnetic forces.’ (emphasis added)].
[See para. 0129 disclosing: ‘"Separating a sample component from a (fluid) sample" means separating a sample component from other components of the original sample, or from components of the sample that are remaining after one or more processing steps. "Removing a sample component from a (fluid) sample" means removing a sample component from other components of the original sample, or from components of the sample that are remaining after one or more processing steps.’ (emphasis added)].
[See para. 0130 disclosing: ‘"Capture" is a type of separation in which one or more moieties or sample components is retained in or on one or more areas of a surface, chamber, chip, bead particles, tube, or any vessel that contains a sample, where the remainder of the sample can be removed from that area.’ (emphasis added)].
[See para. 0132] disclosing: ‘A "binding assay" is an assay that tests for the presence or concentration of an entity by detecting binding of the entity to a specific binding member, or that tests the ability of an entity to bind another entity, or tests the binding affinity of one entity for another entity. An entity can be an organic or inorganic molecule, a molecular complex that comprises, organic, inorganic, or a combination of organic and inorganic compounds, an organelle, a virus, or a cell. Binding assays can use detectable labels or signal generating systems that give rise to detectable signals in the presence of the bound entity. Standard binding assays include those that rely on nucleic acid hybridization to detect specific nucleic acid sequences, those that rely on antibody binding to entities, and those that rely on ligands binding to receptors.’]
[See para. 0176 disclosing: ‘The specific binding member that is used to remove WBCs can be used in a solution or can be bound to a solid surface such as a particle. The specific binding member can be bound directly or indirectly to a solid surface. For example, the specific binding member can be bound indirectly to a solid surface through another binding pair, e.g., a biotin-avidin/strepavidin binding pair. The specific binding member can be bound to a solid surface with or without any prior chemical modification(s) and/or conjugation to any molecules such as a member of separate binding pair. Any suitable solid surface can be used. For example, a specific binding member can be bound to a magnetic particle and the RBCs and/or WBCs bound to the magnetic particle can be removed from a blood sample using a magnetic field or force.]
Claim 8 also recites the following:
wherein, when the controller executes the positive separation process, the pipette pump is used to inject the first magnetic bead reagent into the sample,
and when the controller executes the negative separation process, the pipette pump is used to inject the second magnetic bead reagent into the sample.
[See Lin in para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)].
[See para. 0158 disclosing: ‘Frequently, the selective binding member is an antibody or antibody fragment that is selective for a cell surface marker that is associated with a non-target cell and is expected to be absent on the target cells. An example of such markers would be a surface antigen that occurs on one or more types of hematopoietic cells, when the target cell is a non-hematopoietic cell. The solid surface can be a surface of a container that the sample is placed in, or a surface of a swab or other item to be passed through the sample, or it can be a finely divided material such as a bead or gel that can be admixed with the sample. In each case, the sample is exposed to the solid surface for a sufficient period of time to permit binding of the non-target cell type to be removed to the specific binding member; then the sample is separated from the solid surface for further enrichment or analysis. In one preferred embodiment, the solid surface is a plurality of beads, such as magnetic beads, that provide a high surface area for affixing the specific binding member of interest, can be efficiently mixed with the sample to permit binding of the non-target cell to the specific binding material, and can be conveniently separated from the sample to remove the non-target cells.’ (emphasis added)].
[See para. 0164 disclosing: ‘the immuno-particles could be any solid phase particle or microspheres such as magnetic particle, sepharose, sephadex, and agarose etc based particles, and the particles can be chemically modified to conjugate to an antibody or any other specific binding members for selection and binding of non-target cell types to be removed as part of the process for enrichment of the sample in the target cell type of interest.’ (emphasis added)].
[See para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)]
[See para. 0178 disclosing: ‘To further enrich the tumor cells to be assessed, the present methods can further comprise removing a component(s) other than the RBCs and WBCs. For example, the present methods can comprise removing platelets, stem cells, stromal cells, endothelial cells or soluble proteins from the blood sample. The removal of the RBCs and WBCs and the removal of the other undesirable component(s) can be carried out in separate steps or in the same step. Methods for such removal could include those described below as well as others known to those skilled in the art.’ (emphasis added)].
Claim 8 also recites:
providing a magnetic separation rack to generate a magnetic field to enrich the target biosubstances so as to separate the target biosubstances and the non-target biosubstances; and
[See Lin in para. 0180 disclosing that an RBC lysis buffer is added, and the sample is incubated with rotation at room temperature for about 8 min. Following the lysis of the red blood cells the sample is centrifuged; the supernatant is aspirated, leaving remaining cell pellet undisturbed. The cell pellet is completely resuspended…The cell suspension is transferred into a tube, and magnetic beads slurry is added. The beads are coated with antibody recognizing the CD50 antigen. The cells/beads suspension is incubated with gentle rotation. Following the incubation, the tube is positioned on a magnetic stand to allow for the beads and the non-cancer cells adsorbed to the beads to migrate towards the side of the tube facing the magnet…]
[See para. 0182 disclosing that beads are coated with antibodies recognizing CD50, and optionally CD34 and CD31 and CD235a antigens. The cells/beads suspension is incubated with rotation. Following the incubation, the tube is positioned on a magnetic stand to allow for the beads and the hematopoietic cells adsorbed to the beads to migrate towards the side of the tube facing the magnet].
[See para. 0239 disclosing that an RBC lysis buffer is added, and the sample is incubated with rotation at room temperature for about 8 min. Following the lysis of the red blood cells the sample is centrifuged; the supernatant is aspirated, leaving the remaining cell pellet undisturbed; the cell pellet is completely resuspended; the cell suspension is transferred into a tube and beads slurry is added. The beads are coated with antibody recognizing the CD50 antigen. The cells/beads suspension is incubated with rotation. Following the incubation, the tubes are positioned on a magnetic stand to allow for the beads and the non-cancer cells adsorbed to the beads to migrate towards the side of the tube facing the magnet.]
Claim 8 also recites:
providing the pipette pump to separate the target biosubstances and the non-target biosubstances,
wherein, when the controller executes the positive separation process, the pipette pump is used to suction and capture the target biosubstances,
and when the controller executes the negative separation process, the pipette pump is used to suck away and remove the non-target biosubstances and leave the target biosubstances.
[See Lin in para. 0068 positive-selection cell isolation methods known in the art, such as those that select the target cell from a biological fluid or sample by exposing the sample to a plurality of magnetic beads coated with a specific binding member that binds to a surface marker on the target cell].
[See para. 0070 disclosing: “The enriched samples can be characterized and/or further manipulated in a downstream process performed on a miniaturized microfluidic device, such as a microfluidic chip or cartridge. Such device may comprise one or more elements that use the principle(s) of dielectrophoresis, thermal gradient, acoustic, electroosmosis, or electromagnetic manipulation. Such device may also comprise filtration, mixing, sonication, thermal cycling, immunomagnetic separation, nucleic acid hybridization, two-photon microscopy, absorbance-based detection, fluorescence-based detection, FRET-based detection, immunorecognition, impedance measurement, electrical field stimulation, or cell culture functions. One preferred embodiment of the present invention involves obtaining a sample enriched by a method described in the present invention, loading the enriched sample onto a microfluidic device that then separates rare cells of interest from the rest of the cells in the sample, directing the separated cells to individual culture chambers for incubation, subjecting each culture chambers to therapeutic agents to be tested, and generating a suitable readout that is useful to evaluate the effects of the therapeutic agents.” (Emphasis added).]
[See para. 0088 disclosing: ‘As used herein, "manipulation" refers to moving or processing of the moieties, which results in one-, two- or three-dimensional movement of the moiety, whether within a single chamber or on a single chip, or between or among multiple chips and/or chambers. Moieties that are manipulated by the methods of the present invention can optionally be coupled to binding partners, such as microparticles. Non-limiting examples of the manipulations include transportation, capture, focusing, enrichment, concentration, aggregation, trapping, repulsion, levitation, separation, isolation or linear or other directed motion of the moieties. For effective manipulation of moieties coupled to binding partners, the binding partner and the physical force used in the method must be compatible. For example, binding partners with magnetic properties must be used with magnetic force. Similarly, binding partners with certain dielectric properties, e.g., plastic particles, polystyrene microbeads, must be used with dielectrophoretic force.’]
Claim 9 recites that the positive separation process includes:
providing the pipette pump to inject the first magnetic bead reagent into the sample;
providing an oscillator to perform a mixing process, such that the first immunomagnetic beads binds to the target biosubstances in the sample
[See Lin in para. 0180 disclosing: A sample of blood is centrifuged, the supernatant are discarded and the pellet is completely resuspended by gentle shaking. An RBC lysis buffer is added, and the sample is incubated with rotation [equivalent to Applicant’s oscillation]. Following the lysis of the red blood cells the sample is centrifuged, the supernatant is aspirated, leaving remaining cell pellet, then resuspending the pellet. The cell suspension is transferred into a tube, and magnetic beads slurry is added. The beads are coated with antibody recognizing the CD50 antigen. The cells/beads suspension is incubated with gentle rotation.]
[See para. 0182 that cells/beads suspension is incubated with gentle rotation, and following the incubation, the tube is positioned on a magnetic stand to allow for the beads and the hematopoietic cells adsorbed to the beads to migrate towards the side of the tube facing the magnet].
[See para. 0239 disclosing an RBC lysis buffer is added, and the sample is incubated with rotation…The beads are coated with antibody recognizing the CD50 antigen. The cells/beads suspension is incubated with gentle rotation for 20 minutes at room temperature. Following the incubation, the tubes are positioned on a magnetic stand to allow for the beads and the non-cancer cells adsorbed to the beads to migrate towards the side of the tube facing the magnet.]
Claim 9 also recites:
providing the magnetic separation rack to magnetically attract the first immunomagnetic beads and enrich the target biosubstances so as to separate the target biosubstances and the non-target biosubstances in the sample;
providing the pipette pump to suck and remove the non-target biosubstances;providing the pipette pump to inject a elution buffer into the sample, such that the first immunomagnetic beads are separated from the target biosubstances;providing the magnetic separation rack to magnetically attract the first immunomagnetic beads so as to separate the first immunomagnetic beads and the target biosubstances; and
providing the pipette pump to suck and capture the target biosubstances.
[See Lin in para. 0180 disclosing an RBC lysis buffer is added, and the sample is incubated with rotation. Following the lysis of the red blood cells the sample is centrifuged. The supernatant is aspirated, leaving remaining cell pellet. The cell pellet is completely resuspended. The cell suspension is transferred into a 2 tube, and magnetic beads slurry is added. The beads are coated with antibody recognizing the CD50 antigen. The cells/beads suspension is incubated with gentle rotation for 5 to 60 minutes at room temperature. Following the incubation, the tube is positioned on a magnetic stand to allow for the beads and the non-cancer cells adsorbed to the beads to migrate towards the side of the tube facing the magnet.]
Claim 10 recites that the negative separation process includes:
providing the pipette pump to inject a second magnetic bead reagent into the sample and providing an oscillator to perform a mixing process, such that the second immunomagnetic beads binds to the target biosubstances;
providing the magnetic separation rack to magnetically attract the second immunomagnetic beads and enrich the target biosubstances so as to separate the target biosubstances and the non-target biosubstances in the sample;
and providing the pipette pump to suck and remove the non-target biosubstances and leave the target biosubstances.
[See Lin in para. 0145 disclosing: ‘"Continuous flow" means that fluid is pumped or injected into a chamber of the present invention continuously during the separation process. This allows for components of a sample that are not selectively retained in a chamber to be flushed out of the chamber during the separation process.’]
[See paras. 0029, 0037 disclosing that the microparticle may comprise a magnetic material to facilitate separation of the particle from the enriched sample].
[See paras. 0042 disclosing magnetic capture methods].
[See para. 0046 disclosing: “removing the remaining hematopoietic cells such as white blood cells (WBCs) by specific binding of said hematopoietic cells to specific binding members, such as binding WBCs to an anti-CD50 antibody or another leukocyte-specific antibody, which may be linked to a solid surface such as a microparticle or a magnetic particle, to enrich the sample with the targeted cancer cells, if any are present”].
[See para. 0048 disclosing, “Suitable means for removing WBCs are also disclosed herein, and include, for example microparticles that are optionally magnetic and are linked to at least one specific binding member that is selective for binding to leukocyte surface antigens.”]
[See para. 0092 disclosing: ‘As used herein, "the moiety to be manipulated is substantially coupled onto surface of the binding partner" means that a percentage of the moiety to be manipulated is coupled onto a surface of the binding partner and can be manipulated by a suitable physical force via manipulation of the binding partner…’ (emphasis added)].
[See para. 0128: disclosing: ‘"Separation" is a process in which one or more components of a sample are spatially separated from one or more other components of a sample. A separation can be performed such that one or more sample components of interest is translocated to or retained in one or more areas of a separation apparatus and at least some of the remaining components are translocated away from the area or areas where the one or more sample components of interest are translocated to and/or retained in, or in which one or more sample components is retained in one or more areas and at least some or the remaining components are removed from the area or areas. Alternatively, one or more components of a sample can be translocated to and/or retained in one or more areas and one or more sample components can be removed from the area or areas. It is also possible to cause one or more sample components to be translocated to one or more areas and one or more sample components of interest or one or more components of a sample to be translocated to one or more other areas. Separations can be achieved through, for example, filtration, or the use of physical, chemical, electrical, or magnetic forces. Nonlimiting examples of forces that can be used in separations are gravity, mass flow, dielectrophoretic forces, traveling-wave dielectrophoretic forces, and electromagnetic forces.’ (emphasis added)].
[See para. 0129 disclosing: ‘"Separating a sample component from a (fluid) sample" means separating a sample component from other components of the original sample, or from components of the sample that are remaining after one or more processing steps. "Removing a sample component from a (fluid) sample" means removing a sample component from other components of the original sample, or from components of the sample that are remaining after one or more processing steps.’ (emphasis added)].
Claim 11 recites that when the sample is blood, the negative separation process further includes:
providing the pipette pump to inject a lysis buffer to the sample for performing a lysis process, so as to lyse red blood cells in the non-target biosubstances.
[See Lin in para. 0102 disclosing: A `desired cell` or `target cell` is a specific type of rare cell of interest that might be identified and/or separated and/or enriched from other types of cells by methods involving a marker or property that is preferentially present or absent on the desired or target cells. Cells that are desirably removed in order to facilitate the identification, isolation, or characterization of a target cell are referred to as "non-target cells", and a biological sample may contain multiple types of non-target cells; accordingly, the methods of the invention can be used in various combinations to remove different non-target cells. For example, more than one type of cell may be removed by use of one or more selective lysis steps; more than one type of non-target cell may be removed by selective binding to a solid support, and this may involve individual steps, each using a specific binding member to remove one cell type, or it may involve a single processing step where the sample is exposed to more than one specific binding member adhered to one or more solid surfaces, to effect removal of more than one type of non-target cell in one step.]
[See para. 0156 disclosing: In some embodiments, the enrichment of the target cell(s) in the sample is achieved in a series of steps. One step in the sequence may be a selective lysis step, which uses osmotic pressure change to selectively lyse certain types of cells, such as red blood cells, without lysing the target cell. That enables the removal of at least one type of non-target cell, so that the remaining cell population in the sample is enriched in the target cell.]
[See para. 0174 disclosing: The RBCs can be removed from a blood sample by any suitable methods. For example, the RBCs can be removed by sedimentation, filtration, selective lysis, or binding to a specific binding member that specifically binds RBCs a combination of the above, and/or repetition of the above. In some preferred embodiments, RBCs are removed from a blood sample by lysing them by conventional methods, such as exposing them to a medium or buffer known to selectively lyse RBCs without lysing the target cells of interest.]
[See paras. 0180 and 0182 disclosing the addition of an RBC lysis buffer.]
[See para. 0176 disclosing: ‘The specific binding member that is used to remove WBCs can be used in a solution or can be bound to a solid surface such as a particle. The specific binding member can be bound directly or indirectly to a solid surface. For example, the specific binding member can be bound indirectly to a solid surface through another binding pair, e.g., a biotin-avidin/strepavidin binding pair. The specific binding member can be bound to a solid surface with or without any prior chemical modification(s) and/or conjugation to any molecules such as a member of separate binding pair. Any suitable solid surface can be used. For example, a specific binding member can be bound to a magnetic particle and the RBCs and/or WBCs bound to the magnetic particle can be removed from a blood sample using a magnetic field or force.]
[See para. 0176 disclosing: ‘The specific binding member that is used to remove WBCs can be used in a solution or can be bound to a solid surface such as a particle. The specific binding member can be bound directly or indirectly to a solid surface. For example, the specific binding member can be bound indirectly to a solid surface through another binding pair, e.g., a biotin-avidin/strepavidin binding pair. The specific binding member can be bound to a solid surface with or without any prior chemical modification(s) and/or conjugation to any molecules such as a member of separate binding pair. Any suitable solid surface can be used. For example, a specific binding member can be bound to a magnetic particle and the RBCs and/or WBCs bound to the magnetic particle can be removed from a blood sample using a magnetic field or force.]
[See para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)].
Claim 12 recites that when the target biosubstances include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or microRNA (miRNA), the controller executes the positive separation process.
[See Lin in para. 0016 disclosing: The present methods utilize a negative or depletion approach for isolating rare cells from a sample. In these methods, a sample is progressively enriched for the rare cells of interest by a series of steps that remove other components from the sample with high specificity. Target cells, such as circulating tumor cells in blood samples, mesenchymal cells, epithelial cells, stem cells,…]
[See para. 0067 disclosing telomerase activity assay can be used to further characterize circulating tumor cells isolated with the depletion methods of the present invention or with positive selection methods well known to those skilled in the arts.]
Claim 12 also recites that when the target biosubstances include white blood cells (WBCs), the controller executes the negative separation process.
[See Lin in para. 0048 disclosing, “Suitable means for removing WBCs are also disclosed herein, and include, for example microparticles that are optionally magnetic and are linked to at least one specific binding member that is selective for binding to leukocyte surface antigens.”]
[See para. 0176 disclosing: a specific binding member can be bound to a magnetic particle and the RBCs and/or WBCs bound to the magnetic particle can be removed from a blood sample using a magnetic field or force.]
[See para. 0177 disclosing: ‘The RBCs and WBCs can be removed from a blood sample in any suitable order. For example, the RBCs can be removed before the WBCs are removed from the blood sample. In another example, the WBCs are removed before the RBCs are removed from the blood sample. In still another example, the RBCs and WBCs can be removed from a blood sample simultaneously.’ (emphasis added)]
Claim Rejections - 35 USC § 103
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) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20080057505 (hereinafter “Lin”).
Claim 14 recites that the step of providing the magnetic separation rack to generate the magnetic field to enrich the target biosubstances so as to separate the target biosubstances and the non-target biosubstances further includes:
providing two magnets mounted on the magnetic separation rack to apply the magnetic field to the sample,
wherein the two magnets have opposite magnetic properties,
two surfaces of the two magnets have an included angle therebetween that ranges from 90 degrees to 180 degrees, and the two magnets are spaced apart from each other by a gap that ranges from 2.5 mm to 5.5 mm.
Lin, discussed above, while disclosing use of magnets (see for example discussion of claim 8 above), is silent as to two surfaces of the two magnets have an included angle therebetween that ranges from 90 degrees to 180 degrees, and the two magnets are spaced apart from each other by a gap that ranges from 2.5 mm to 5.5 mm.
However, Lin does disclose use of one or more permanent magnets (para. 0122), and that the microparticles have a dimension that is in the micron to micrometer range (para. 0147).
More specifically, Lin discloses the following in paragraph 0122.
‘An "automated system for separating rare cells from a fluid sample" or an "automated system" is a device that comprises at least one filtration chamber, automated means for directing fluid flow through the filtration chamber, and at least one power source for providing fluid flow and, optionally, means for providing a signal source for the generation of forces on active chips. An automated system of the present invention can also optionally include one or more active chips, separation chambers, separation columns, or permanent magnets.” (Emphasis added].
‘A ‘"microparticle" is a structure of any shape and of any composition that is manipulatable by desired physical force(s). The microparticles used in the methods could have a dimension from about 0.01 micron to about ten centimeters. Preferably, the microparticles used in the methods have a dimension from about 0.1 micron to about several hundred microns. Such particles or microparticles can be comprised of any suitable material, such as…magnetic beads, magnetic particles…’ (para. 0147, emphasis added)].
Thus while Lin is silent as to two surfaces of the two magnets having an included angle therebetween that ranges from 90 degrees to 180 degrees, and the two magnets are spaced apart from each other by a gap that ranges from 2.5 mm to 5.5 mm, such ranges fall within a workable or optimum range. Discovering a workable or optimum range requires ordinary skills in the art where the general conditions of the claims are disclosed, such as in this case as disclosed by Lin, since it merely modifies the parameters (such as distance or angle) of known element(s) (such as the magnets) to achieve a result disclosed by Lin.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20080057505 (hereinafter “Lin”) in view of US 20150224499 (hereinafter “Wang”).
Claim 13 recites providing a pressure sensor to detect a pressure change in the pipette pump.
While Lin is silent as to this limitation, Wang teaches it.
More specifically, Wang teaches the following.
Wang teaches an automated assay platform for determining the presence and/or amount of analytes of interest in a sample integrates microfluidic enhanced assay sites, disposable cartridge designs, a sensitive low-volume detection module, together with selected pumping and valving modules, customized control board and user friendly graphical user interface (GUI). (See abstract.)
Wang teaches that several sensors are also integrated for real time assay monitoring and troubleshooting. The sensors include but are not limited to flow sensor, pressure sensor and temperature sensor. An inline flow sensor is very useful to provide real time flow information during the assay and could detect variations caused by clogging, bubbles and valve operations. A pressure sensor that connected to the fluidic system through a manifold could also provide real time flow information to prevent clogging and potential leakage during the assay…” Para. 0046 (emphasis added).
It would have been obvious to one skilled in the art to provide a pressure sensor in the Lin chip in order to provide real time flow information to prevent clogging and potential leakage during an assay, as taught by Wang.
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678