DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-38 are pending in this application.
Applicant’s amendment to the claims filed 12/22/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 12/22/2025 is acknowledged.
Applicant’s amendment to the drawings filed 12/22/2025 is acknowledged.
Applicants Declaration under 37 CFR 1.130 filed 12/22/2025 is acknowledged and has been fully considered.
Applicant’s remarks filed on 12/22/2025 in response to the non-final rejection mailed on 07/22/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Invention I, corresponding to claims 1-8, 12 and 29-38, drawn to a method of isolation of cellular nuclei comprising loading a sample comprising cell nuclei and a sample medium comprising mixing a sample with a paramagnetic compound, subjecting the sample to magnetic force, and optionally imaging fractions of the separated sample, classified in CPC G01N 1/40
elected with traverse in the reply filed 04/07/2025.
The Requirement for Restriction mailed 02/07/2025 established Invention I corresponding to claims 1-8 and 12-26, and Invention II corresponding to claims 9-11 and 27-28. Applicant stated in the reply filed 04/07/2025 that claims 13-26 in the original filing were intended to depend from claim 9, and therefore should be included with Invention II. As such, Applicant notes the election of the Invention I, corresponding to claims 1-8, 12 and 29-38. Applicant’s correction is acknowledged, and Applicant should consider amending the claims to make the noted corrections where appropriate. For example, as claim 12 is drawn to a method of recovering both live cells and nuclei, Applicant may consider whether claim 12 was also meant to depend from claim 9.
Claims 9-11 and 13-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 with traverse in the reply filed on 04/07/2025.
Claims 1-8, 12 and 29-38 are being examined on the merits.
Priority
The instant application claims domestic priority to U.S. Application 63/139,301 filed 01/19/2021.
In view of the amendment to claim 1, the disclosure of the prior-filed application, Application No. 63/139,301, is considered to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a), and accordingly, claim 1 and its dependent claims 2-8, 12 and 29-38 are entitled to the benefit of the prior application.
Claims 1-8, 12 and 29-38 have an effective filing date of 01/19/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 12/22/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Objections to Specification
The disclosure is objected to because of the following informalities.
The use of the terms CELLOMETER and RNASEOUT, which are trade names or marks used in commerce, have been noted in this application in paragraphs 00223. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Response to Remarks: beginning on page 14 of Applicant’s response to specification objections; Applicant in summary contends the present amendments address the objections of record.
Applicant’s remarks are considered and found not convincing, as the objection to the use of the trade names or marks described in the objection above has not been addressed.
Objections to Drawings
The objections to the drawings are withdrawn in view of the amendment to Figure 28 to label the panels in accordance with the description of the figure in the specification.
Claim Objections
The objection to claim 1 is withdrawn in view of the amendment to recite “loading a sample comprising a cell nuclei from lysed cells and a sample medium into a separation channel, wherein the sample medium comprises a paramagnetic compound”.
The objections to claims 2-8 and 36-38 are withdrawn in view of the amendments to recite “The method of claim” consistent with the preamble of claims 29-34.
Claim 35 is objected to for the phrase “A method according to claim 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “The method of claim 1” to be consistent with the preamble of claims 2-8, 29-34, and 36-38.
Response to Remarks: beginning on page 14 of Applicants response to claim objections; Applicant in summary contends the claims have been amended to overcome the objections of the previous office action.
Applicant’s remarks are considered and found not convincing, as claim 35 has not been amended to address the objection previously set forth.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-2, 4, and 33-35 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention are withdrawn in view of
the amendment to claim 1 to recite “without centrifugation”,
the amendments to claims 2, 33 and 34 to no longer recite the relative term “about”, and
the amendments to claims 4 and 35 to recite “the loaded sample”.
Claims 5-6, 12, and 36 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claims 5, 12 and 36 recite the limitations “the concentration of non-nuclei particles” (claims 5 and 36), “the total nuclei” and “the yield” (claim 12), and “the original sample” (claim 36)”. There is insufficient antecedent basis for these limitations in the claims.
Claim 6 is indefinite for the limitation “the integrity of isolated cell nuclei … is … greater than the integrity of cell nuclei isolated … by a method comprising centrifugation”. As written, it is unclear what steps are to be included in the reference method for comparison, as the reference method comprising centrifugation is unlimited.
Claim 12 is indefinite for the phrase “the method of claim 1, wherein the yield of nucleic is at least …75% of the total nuclei from the loaded sample”. As claim 1 does not recite “yield”, it is unclear how one of skill in the art is intended to determine the yield recited in the phase. Put another way, it is unclear what is being compared to the total nucleic from the loaded sample in order to determine the yield recited in the claim.
Response to Remarks: beginning on page 15 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends regarding the rejection of claim 6 that the specification at [para 00219] defines integrity as integrity of the nuclear membrane resulting in containment of a substantial portion of DNA and RNA within the isolated nuclei, and that such containment is well known in the art; Applicant further contends regarding claim 6 that the a comparative method for centrifugation is well known in the art; Applicant further contends the instant amendments to the claims overcome the rejections of record.
Applicant’s remarks are considered and found not convincing. Regarding claim 6, while Applicant’s disclosure in the specification at [para 00219] sets forth a definition for “integrity”, and the claims recite a level of integrity to be measured, the claims do not recite any limitations regarding the reference method for comparison aside from the reference method comprises centrifugation. While Applicant has provided standard methods from the art for isolating cell nuclei, the reference method for comparison recited in the claims is considered unlimited aside from the centrifugation.
The rejection of claims 5, 12 and 36 are maintained in view of the reasons stated in the rejection above.
Claim Rejections - 35 USC § 102
The rejection of claims 1-4, 12, 29-32 and 35 under 35 U.S.C. 102(a)(1) as being anticipated by Plouffe et al. (Rep Prog Phys, 2015, 78:016601; cited on the Form PTO-892 mailed 07/22/2025; herein referred to as Plouffe) is withdrawn in view of the amendment to claim 1 to recite “isolation of nuclei from lysed cells”.
Claim Rejections - 35 USC § 103
The rejection of claim 6 under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Nagata et al. (Anal Biochem, 2010, 398: 178; cited on the Form PTO-892 mailed 07/22/2025; herein referred to as Nagata), and
the rejection of claims 33-34 under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Paul et al. (British J Haemotol, 1978, 38:273; cited on the Form PTO-892 mailed 07/22/2025; herein referred to as Paul)
are withdrawn in view of the amendment to claim 1 to recite “isolation of nuclei from lysed cells”.
Claims 1-5, 7-8, 12 and 35-38 are rejected under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Ma et al. (Jove, 2014, 85:e51418; cited on the Form PTO-892 mailed 07/22/2025; herein referred to as Ma).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 1 is drawn to a method of isolation of nuclei from lysed cells, comprising
loading a sample comprising cell nuclei from lysed cells and a sample medium into a separation channel, wherein the sample medium comprises a paramagnetic compound;
subjecting the loaded sample to a magnetic force with at least one magnet to affect a separation;
collecting at least one fraction of the separated sample comprising cell nuclei without centrifugation and;
optionally imaging the nuclei in the sample prior to, during, and/or after the separation.
Plouffe reviews the fundamentals and application of magnetic particles in cell isolation and enrichment [title].
Regarding claim 1 and the limitation of subjecting a loaded sample to a magnetic force to affect a separation in a separation channel, and collecting at least one fraction of a separated sample without centrifugation, Plouffe discloses the separation of biological cells is critical to a variety of biomedical applications [p 1, col 1, para 1], and discloses magnetic separation techniques based on cell affinity that describes magnetic properties to a cell type [p 1, col 2, para 1]. Plouffe describes the process of magnet-activated cell sorting (MACS) [p 2, col 1, para 1], wherein antibody-mediated techniques comprising magnetic particle tags are used to isolate specific cells in a sample [p 3, col 1, para 2] as described in [Table 1]. Plouffe outlines a magnetic labeling method of cells in [Figure 3A] which shows a target cell in a sample is preferentially labeled with a magnetic nanoparticle (MNP, or magnetic bead) and subjected to a magnetic field while the sample flows through a separation channel [Figure 3D] for separation of the target molecule from the sample, wherein the depiction in [Figure 3D] is considered to correspond to the collection of a fraction of a separated sample without centrifugation.
Regarding claim 1 and the limitation wherein the sample comprises a paramagnetic compound, Plouffe describes that regarding magnetizable carrier fluids, a situation can result from an extreme excess concentration of magnetic beads within the system such that the carrier fluid is a ferrofluid [p 22, col 2, para 1], wherein a ferrofluid is considered to be encompassed by the term “paramagnetic compound”.
Plouffe does not teach the separation of nuclei from lysed cells.
Ma relates to affinity-based isolation of tagged nuclei from Drosophila tissues [title], and discloses it can be necessary to isolate specific cell types with high purity, however cell morphology can be irregular in tissues which may pose challenges for isolation which can be overcome using systems to isolate nuclear envelope localized tags [abstract].
Regarding claim 1 and the limitations regarding the separation of nuclei from lysed cells, Ma teaches a method that adapts the “isolation of nuclei tagged in specific cell types” (INTACT) wherein a nuclear envelope fusion protein can be biotinylated for purification of the nuclei in mixed populations [p 1, para 2 of “Introduction”]. Ma describes the modification of this INTACT method wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads, wherein nuclei were isolated in the present of nonionic detergent to remove the outer [p 2, para 1]. Ma therefore describes nuclei isolated from samples prepared as described in Section 2 at the end of page 2, specifically steps 3-4 that encompass the disruption of tissue to produce a homogenate containing nuclei and cellular debris [page 3, top], which is considered to correspond to the isolation of nuclei from lysed cells.
In view of Ma, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Plouffe by using nuclear-envelope fusions to isolate nuclei from lysed cells, as taught by Ma, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Plouffe, because Ma teaches a method to isolate specific cell types with high purity using systems to isolate nuclear envelope localized tags that overcomes the challenge imposed on isolations otherwise relying on cell morphology alone. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Ma discuss affinity-based isolation methods of biological samples comprising magnetic separation.
Regarding claim 2, Plouffe discloses a method that can provide high cell purities at high throughput of approximately 1010 cells h-1 [p 11, col 2, para 1], which is interpreted to correspond to the upper limit of reliable throughput of a sample, and therefore that the method of Plouffe is carried out on samples up to 1010 cells h-1 in a sample. As such, the disclosure of Plouffe is considered to correspond to a sample comprising 50 – 108 cell nuclei.
Regarding claim 3, Plouffe outlines the method in [Figure 3A], wherein the depicted cells are considered to correspond to live or dead cells, and the method of Ma is carried out on a homogenate that includes cellular debris [page 3, top].
Regarding claims 4 and 35, the limitation of “the concentration of cell nuclei in a fraction is increased” is interpreted to correspond to the increase in targeted cell nuclei compared to the sample before the separation step. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to an increase in the concentration of cell nuclei by at least 10% (corresponding to claim 4) and 50% (corresponding to claim 35) from the original sample.
Regarding claims 5 and 36, Ma teaches the modified INTACT method described in the rejection of claim 1 above, wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads [p 2, para 1]. As this combined method of Plouffe and Ma only isolates nuclei, it is considered to correspond to the reduction of non-nuclei particles of 1% (corresponding to claim 5) and 10% (corresponding to claim 36) compared to the original sample.
Regarding claim 7, Ma teaches the method adapted from the INTACT method described above which is carried out in Arabidopsis thaliana [p 1, para 2], which is understood as a plant. As the INTACT method developed for plants, one of skill in the art would be able to carry out the modified INTACT method of Ma in a plant cell.
Regarding claims 8 and 37-38, Ma teaches the method of nuclei isolation carried out on neuronal cell types within the adult brain of Drosophila which implicitly involve genetically modifying the cell types to contain the nuclear envelope fusion protein comprising GFP [p 2, para 1], and therefore corresponds to the isolation of nuclei from brain cells (corresponding to claim 37) and from gene-edited cells (corresponding to claims 8 and 38).
Regarding claim 12, in view of the indefiniteness of the claim, and for the sake of compact prosecution, the claim is being examined under the interpretation that the limitation of “the yield of nuclei in the first recovered sample is at least about 50%...of the total nuclei from the loaded sample” corresponds to the increase in targeted cell nuclei after separation compared to the loaded sample before separation. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to the yield of nuclei being at least 50%.
Therefore, the invention of claims 1-5, 7-8, 12 and 35-38 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 6 is newly rejected under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Nagata.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 6 is drawn to the method of claim 1 wherein the integrity of isolated cell nuclei in a fraction from a sample is at least 30% greater than the integrity of cell nuclei isolated in a fraction from a sample by a method comprising centrifugation.
The teachings of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. These references do not teach the limitations of integrity of cell nuclei.
The instant application defines the term “integrity” as “integrity of the nuclear membrane resulting in containment of a substantial proportion of DNA and RNA within the isolated nuclei” in [para 00219] of the specification.
Nagata relates to the isolation of intact nuclei of high purity [title], and discloses comparisons of nuclear isolation methods using different speeds of centrifugation [abstract].
Regarding claim 6, Nagata discloses that moderate centrifugal force (MCF) yielded higher purity of nuclei, high nuclei number per gram, and higher RNA per gram of sample when compared to high centrifugal force (HCF) [Table 1]. Nagata further teaches that isolated nuclei contained better membrane integrity with MCF than with HCF [p 182, col 1, para 2].
While Nagata does not teach the % difference in integrity between centrifugal and non-centrifugal isolation methods recited in the claim, Nagata identifies centrifugal force as a result effective variable, which is a variable that achieves a recognized result according to MPEP 2144.05.II.B. In view of the teachings of Nagata, one of skill in the art would expect that reducing centrifugal force would improve nuclei integrity, and therefore carrying out the combined method of Plouffe and Ma which lacks centrifugation would result in increased nuclei integrity compared to a method with centrifugation. Furthermore, as the claim does not recite any specific method of isolation comprising centrifugation, one of skill in the art would be able to modify the method of Nagata by increasing the centrifugal speed, thereby decreasing nuclei integrity, in order to achieve the claimed difference in nuclei integrity, as Nagata establishes the result effective variable of centrifugal force that effects the result of nuclei integrity, and therefore the % difference in integrity when comparing nuclei isolation methods lacking and methods comprising centrifugation.
In view of Nagata, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Plouffe and Ma by comparing membrane integrity to a modified method of Nagata to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Plouffe and Ma by comparing to a modified method of Nagata, because Nagata teaches the result effective variable of centrifugal force wherein higher centrifugal force results in lower nuclei integrity. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Nagata relate to methods to isolate cell nuclei from samples.
Therefore, the invention of claim 6 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 29-32 are newly rejected under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Shen et al. (Analyt Chem, 2012, 84: 3075; cited on the attached Form PTO-892; herein referred to as Shen).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 29 is drawn to the method of claim 1, wherein the paramagnetic compound is a paramagnetic material that comprises gadolinium (Gd).
The teachings of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. These references do not teach a paramagnetic material that comprises Gd.
Shen relates to label-free cell separation using a tunable magnetophoretic repulsion force [title].
Regarding claim 29, Shen teaches the difference in magnetic forces acting on different sized cells is enhanced by adjusting the magnetic susceptibility of the surrounding medium, which depends on the concentration of paramagnetic salts, such as biocompatible gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) [abstract].
In view of Shen, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of Plouffe and Ma by using the Gd-DTPA of Shen to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the magnetic beads of Plouffe and the Gd-DTPA of Shen are both paramagnetic compounds, and as such both are capable of being incorporated into magnetic-based separation methods such as those described by Plouffe and Ma. Thus it would have been obvious to one of ordinary skill in the art to replace the magnetic beads of Plouffe with the Gd-DTPA of Shen, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because Plouffe, Ma and Shen related discuss methods to separate biological materials by magnetic means.
Regarding claim 30, the Gd-DTPA of Shen [abstract] is understood to be a gadolinium chelate.
Regarding claims 31-32, Shen teaches solutions of Gd-DTPA with concentrations ranging 0 to 80 mM [p 3077, col, 2, para 2]. According to MPEP 2144.05.I, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Therefore, the invention of claims 29-32 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 33-34 are newly rejected under 35 U.S.C. 103 as being unpatentable over Plouffe in view of Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Paul.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 33 is drawn to the method of claim 1, wherein the magnetic force is a magnetic field with a surface field strength of 0.1 Tesla to 100 Tesla, or between 0.5 Tesla and 2.0 Tesla; or 0.5 Tesla.
The teachings of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. These references do not teach the strength of a magnetic field.
Paul relates to cell separation techniques using high gradient magnetic fields [title], and discloses the magnetic isolation of cells containing hemoglobin without damaging cells or causing hemolysis [abstract] to utilize advantages of magnetic separation over techniques involving specific gravity [p 273, para 1] which is interpreted as techniques involving centrifugation.
Regarding claims 33-34, Paul teaches that applying magnetic field to samples with a strength above 0.5 Tesla corresponds to a separation of target cells that is proportional to the applied magnetic field at all flow rates, and also indicates the use of magnetic field strengths ranging from ~0.3 Tesla to 1.4 Tesla [p 276, para 4; and Figure 2].
In view of Paul, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Plouffe and Ma by applying the magnetic field strengths of Paul to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Plouffe and Ma by applying the magnetic field strengths of Paul, because Paul teaches magnetic isolation of cells has an advantage over techniques involving specific gravity as the magnetic isolation does not damage cells, and additionally shows a range of magnetic field strengths capable of separating cells based on their magnetic properties. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Paul relate to methods of isolating cells based on magnetic properties.
Therefore, the invention of claims 33-34 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on p 15 of Applicant’s response to rejections under 35 USC 102 and 103; Applicant in summary contends Plouffe does not teach or suggest the isolation of cell nuclei from lysed cells, and the other prior art of record do not cure the deficiencies of Plouffe, and as a result the amended claims overcome the previously stated prior art rejections.
Applicant’s remarks are considered and found not convincing. The rejection under 35 USC 102 has been withdrawn in view of the amendment to claim 1 as drawn to a method of isolating cell nuclei from lysed cells. Regarding rejections under 35 USC 103, while Plouffe does not teach the isolation of cell nuclei from lysed cells as stated above, Ma teaches a method of isolating cell nuclei from lysed cells using a modified INTACT method as described in the rejection above. In view of these teachings and those stated in the rejection above, the claims are rejected under 35 USC 103.
Double Patenting
The provisional rejection of Claims 1-4 and 35 on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938,825,
the provisional rejection of Claim 6 on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938,825 in view of Nagata, and
the provisional rejection of Claims 33-34 on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938,825 in view of Paul
are withdrawn in view of the amendment to claim 1 to recite “isolation of nuclei from lysed cells”.
A. Claims 1-5, 7-8, 12 and 35-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938825 (herein “reference application”) in view of Plouffe and Ma.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 1, claim 26 of the reference application recites a particle separation method comprising loading a sample containing particles in a suspension with a paramagnetic compound, exposing the sample to a magnetic field, and removing a portion of the separated particles, and claim 32 of the reference application recites the particles comprise cells or cell nuclei.
The claims of the reference application do not recite the isolation of nuclei from lysed cells.
Plouffe reviews the fundamentals and application of magnetic particles in cell isolation and enrichment [title].
Regarding instant claim 1 and the limitation of subjecting a loaded sample to a magnetic force to affect a separation in a separation channel, and collecting at least one fraction of a separated sample without centrifugation, Plouffe discloses the separation of biological cells is critical to a variety of biomedical applications [p 1, col 1, para 1], and discloses magnetic separation techniques based on cell affinity that describes magnetic properties to a cell type [p 1, col 2, para 1]. Plouffe describes the process of magnet-activated cell sorting (MACS) [p 2, col 1, para 1], wherein antibody-mediated techniques comprising magnetic particle tags are used to isolate specific cells in a sample [p 3, col 1, para 2] as described in [Table 1]. Plouffe outlines a magnetic labeling method of cells in [Figure 3A] which shows a target cell in a sample is preferentially labeled with a magnetic nanoparticle (MNP, or magnetic bead) and subjected to a magnetic field while the sample flows through a separation channel [Figure 3D] for separation of the target molecule from the sample, wherein the depiction in [Figure 3D] is considered to correspond to the collection of a fraction of a separated sample without centrifugation.
Regarding instant claim 1 and the limitation wherein the sample comprises a paramagnetic compound, Plouffe describes that regarding magnetizable carrier fluids, a situation can result from an extreme excess concentration of magnetic beads within the system such that the carrier fluid is a ferrofluid [p 22, col 2, para 1], wherein a ferrofluid is considered to be encompassed by the term “paramagnetic compound”.
Ma relates to affinity-based isolation of tagged nuclei from Drosophila tissues [title], and discloses it can be necessary to isolate specific cell types with high purity, however cell morphology can be irregular in tissues which may pose challenges for isolation which can be overcome using systems to isolate nuclear envelope localized tags [abstract].
Regarding instant claim 1 and the limitations regarding the separation of nuclei from lysed cells, Ma discloses a method that adapts the “isolation of nuclei tagged in specific cell types” (INTACT) wherein a nuclear envelope fusion protein can be biotinylated for purification of the nuclei in mixed populations [p 1, para 2 of “Introduction”]. Ma describes the modification of this INTACT method wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads, wherein nuclei were isolated in the present of nonionic detergent to remove the outer [p 2, para 1]. Ma therefore describes nuclei isolated from samples prepared as described in Section 2 at the end of page 2, specifically steps 3-4 that encompass the disruption of tissue to produce a homogenate containing nuclei and cellular debris [page 3, top], which is considered to correspond to the isolation of nuclei from lysed cells.
In view of Plouffe and Ma, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by using the ferrofluid and magnetic affinity purification method of Plouffe with the nuclear-envelope fusions to isolate nuclei from lysed cells of Ma to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the claims of the reference application, because Plouffe discloses the separation of biological cells is critical to a variety of biomedical applications and provides methods for separating cells using magnetic affinity techniques, and because Ma discloses a method to isolate specific cell types with high purity using systems to isolate nuclear envelope localized tags that overcomes the challenge imposed on isolations otherwise relying on cell morphology alone. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application, Plouffe and Ma discuss isolation methods of cells based comprising magnetic separation.
Regarding instant claim 2, claim 26 of the reference application recites the sample comprises at least 5,000,000 particles, and Plouffe discloses a method that can provide high cell purities at high throughput of approximately 1010 cells h-1 [p 11, col 2, para 1], which is interpreted to correspond to the upper limit of reliable throughput of a sample, and therefore that the method of Plouffe is carried out on samples up to 1010 cells h-1 in a sample.
Regarding instant claim 3, claim 32 of the reference application recites the particles comprise cells, Plouffe outlines the method in [Figure 3A], wherein the depicted cells are considered to correspond to live or dead cells, and the method of Ma is carried out on a homogenate that includes cellular debris [page 3, top].
Regarding instant claims 4 and 35, claim 31 of the reference application recites the concentration of the particle in the removed fractional volume is increased 1.5:1 compared to the concentration of the sample. Additionally, the limitation of “the concentration of cell nuclei in a fraction is increased” is interpreted to correspond to the increase in targeted cell nuclei compared to the sample before the separation step. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to an increase in the concentration of cell nuclei by at least 10% (corresponding to instant claim 4) and 50% (corresponding to instant claim 35) from the original sample.
Regarding instant claims 5 and 36, Ma discloses the modified INTACT method described in the rejection of instant claim 1 above, wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads [p 2, para 1]. As this combined method of the reference application, Plouffe and Ma only isolates nuclei, it is considered to correspond to the reduction of non-nuclei particles of 1% (corresponding to instant claim 5) and 10% (corresponding to instant claim 36) compared to the original sample.
Regarding instant claim 7, Ma discloses the method adapted from the INTACT method described above which is carried out in Arabidopsis thaliana [p 1, para 2], which is understood as a plant. As the INTACT method developed for plants, one of skill in the art would be able to carry out the modified INTACT method of Ma in a plant cell.
Regarding instant claims 8 and 37-38, Ma discloses the method of nuclei isolation carried out on neuronal cell types within the adult brain of Drosophila which implicitly involve genetically modifying the cell types to contain the nuclear envelope fusion protein comprising GFP [p 2, para 1], and therefore corresponds to the isolation of nuclei from brain cells (corresponding to instant claim 37) and from gene-edited cells (corresponding to instant claims 8 and 38).
Regarding instant claim 12, in view of the indefiniteness of the instant claim, and for the sake of compact prosecution, the instant claim is being examined under the interpretation that the limitation of “the yield of nuclei in the first recovered sample is at least about 50%...of the total nuclei from the loaded sample” corresponds to the increase in targeted cell nuclei after separation compared to the loaded sample before separation. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to the yield of nuclei being at least 50%.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 6 is newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938825 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Nagata.
The instant rejection is newly stated and necessitated by claim amendment.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite the limitations of integrity of cell nuclei.
Nagata relates to the isolation of intact nuclei of high purity [title], and discloses comparisons of nuclear isolation methods using different speeds of centrifugation [abstract].
Regarding instant claim 6, Nagata discloses that moderate centrifugal force (MCF) yielded higher purity of nuclei, high nuclei number per gram, and higher RNA per gram of sample when compared to high centrifugal force (HCF) [Table 1]. Nagata further discloses that isolated nuclei contained better membrane integrity with MCF than with HCF [p 182, col 1, para 2].
While Nagata does not disclose the % difference in integrity between centrifugal and non-centrifugal isolation methods recited in the instant claim, Nagata identifies centrifugal force as a result effective variable, which is a variable that achieves a recognized result according to MPEP 2144.05.II.B. In view of the disclosure of Nagata, one of skill in the art would expect that reducing centrifugal force would improve nuclei integrity, and therefore carrying out the combined method of the reference application, Plouffe and Ma which lacks centrifugation would result in increased nuclei integrity compared to a method with centrifugation. Furthermore, as the instant claim does not recite any specific method of isolation comprising centrifugation, one of skill in the art would be able to modify the method of Nagata by increasing the centrifugal speed, thereby decreasing nuclei integrity, in order to achieve the recited difference in nuclei integrity, as Nagata establishes the result effective variable of centrifugal force that effects the result of nuclei integrity, and therefore the % difference in integrity when comparing nuclei isolation methods lacking and methods comprising centrifugation.
In view of Nagata, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Plouffe and Ma by comparing membrane integrity to a modified method of Nagata to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Plouffe and Ma by comparing to a modified method of Nagata, because Nagata discloses the result effective variable of centrifugal force wherein higher centrifugal force results in lower nuclei integrity. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Nagata relate to methods to isolate cell nuclei from samples.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-32 newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938825 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Shen.
The instant rejection is newly stated and necessitated by claim amendment.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite a paramagnetic material that comprises Gd.
Shen relates to label-free cell separation using a tunable magnetophoretic repulsion force [title].
Regarding instant claim 29, Shen discloses the difference in magnetic forces acting on different sized cells is enhanced by adjusting the magnetic susceptibility of the surrounding medium, which depends on the concentration of paramagnetic salts, such as biocompatible gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) [abstract].
In view of Shen, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of the reference application, Plouffe and Ma by using the Gd-DTPA of Shen to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the magnetic beads of Plouffe and the Gd-DTPA of Shen are both paramagnetic compounds, and as such both are capable of being incorporated into magnetic-based separation methods such as those described by Plouffe and Ma. Thus it would have been obvious to one of ordinary skill in the art to replace the magnetic beads of Plouffe with the Gd-DTPA of Shen, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because Plouffe, Ma and Shen related discuss methods to separate biological materials by magnetic means.
Regarding instant claim 30, the Gd-DTPA of Shen [abstract] is understood to be a gadolinium chelate.
Regarding instant claims 31-32, Shen discloses solutions of Gd-DTPA with concentrations ranging 0 to 80 mM [p 3077, col, 2, para 2]. According to MPEP 2144.05.I, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 33-34 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 31-32 of co-pending Application No. 17/938825 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Paul.
The instant rejection is newly stated and necessitated by claim amendment.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite the strength of a magnetic field.
Paul relates to cell separation techniques using high gradient magnetic fields [title], and discloses the magnetic isolation of cells containing hemoglobin without damaging cells or causing hemolysis [abstract] to utilize advantages of magnetic separation over techniques involving specific gravity [p 273, para 1] which is interpreted as techniques involving centrifugation.
Regarding instant claims 33-34, Paul discloses that applying magnetic field to samples with a strength above 0.5 Tesla corresponds to a separation of target cells that is proportional to the applied magnetic field at all flow rates, and also indicates the use of magnetic field strengths ranging from ~0.3 Tesla to 1.4 Tesla [p 276, para 4; and Figure 2].
In view of Paul, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Plouffe and Ma by applying the magnetic field strengths of Paul to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Plouffe and Ma by applying the magnetic field strengths of Paul, because Paul discloses magnetic isolation of cells has an advantage over techniques involving specific gravity as the magnetic isolation does not damage cells, and additionally shows a range of magnetic field strengths capable of separating cells based on their magnetic properties. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Paul relate to methods of isolating cells based on magnetic properties.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
B. Claims 1-5, 7-8, 12 and 35-38 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 62 of co-pending Application No. 19/203107 (herein “reference application”) in view of Plouffe and Ma.
The instant rejection is newly stated as a result of the filing of the reference application.
Regarding instant claim 1, claim 8 of the reference application recites a method of isolation of a target subcellular component, and claim 62 recites the target subcellular component is cell nuclei.
The claims of the reference application do not recite the isolation of nuclei from lysed cells.
Plouffe reviews the fundamentals and application of magnetic particles in cell isolation and enrichment [title].
Regarding instant claim 1 and the limitation of subjecting a loaded sample to a magnetic force to affect a separation in a separation channel, and collecting at least one fraction of a separated sample without centrifugation, Plouffe discloses the separation of biological cells is critical to a variety of biomedical applications [p 1, col 1, para 1], and discloses magnetic separation techniques based on cell affinity that describes magnetic properties to a cell type [p 1, col 2, para 1]. Plouffe describes the process of magnet-activated cell sorting (MACS) [p 2, col 1, para 1], wherein antibody-mediated techniques comprising magnetic particle tags are used to isolate specific cells in a sample [p 3, col 1, para 2] as described in [Table 1]. Plouffe outlines a magnetic labeling method of cells in [Figure 3A] which shows a target cell in a sample is preferentially labeled with a magnetic nanoparticle (MNP, or magnetic bead) and subjected to a magnetic field while the sample flows through a separation channel [Figure 3D] for separation of the target molecule from the sample, wherein the depiction in [Figure 3D] is considered to correspond to the collection of a fraction of a separated sample without centrifugation.
Regarding instant claim 1 and the limitation wherein the sample comprises a paramagnetic compound, Plouffe describes that regarding magnetizable carrier fluids, a situation can result from an extreme excess concentration of magnetic beads within the system such that the carrier fluid is a ferrofluid [p 22, col 2, para 1], wherein a ferrofluid is considered to be encompassed by the term “paramagnetic compound”.
Ma relates to affinity-based isolation of tagged nuclei from Drosophila tissues [title], and discloses it can be necessary to isolate specific cell types with high purity, however cell morphology can be irregular in tissues which may pose challenges for isolation which can be overcome using systems to isolate nuclear envelope localized tags [abstract].
Regarding instant claim 1 and the limitations regarding the separation of nuclei from lysed cells, Ma discloses a method that adapts the “isolation of nuclei tagged in specific cell types” (INTACT) wherein a nuclear envelope fusion protein can be biotinylated for purification of the nuclei in mixed populations [p 1, para 2 of “Introduction”]. Ma describes the modification of this INTACT method wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads, wherein nuclei were isolated in the present of nonionic detergent to remove the outer [p 2, para 1]. Ma therefore describes nuclei isolated from samples prepared as described in Section 2 at the end of page 2, specifically steps 3-4 that encompass the disruption of tissue to produce a homogenate containing nuclei and cellular debris [page 3, top], which is considered to correspond to the isolation of nuclei from lysed cells.
In view of Plouffe and Ma, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by using the ferrofluid and magnetic affinity purification method of Plouffe with the nuclear-envelope fusions to isolate nuclei from lysed cells of Ma to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the claims of the reference application, because Plouffe discloses the separation of biological cells is critical to a variety of biomedical applications and provides methods for separating cells using magnetic affinity techniques, and because Ma discloses a method to isolate specific cell types with high purity using systems to isolate nuclear envelope localized tags that overcomes the challenge imposed on isolations otherwise relying on cell morphology alone. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application, Plouffe and Ma discuss isolation methods of cells based comprising magnetic separation.
Regarding instant claim 2, Plouffe discloses a method that can provide high cell purities at high throughput of approximately 1010 cells h-1 [p 11, col 2, para 1], which is interpreted to correspond to the upper limit of reliable throughput of a sample, and therefore that the method of Plouffe is carried out on samples up to 1010 cells h-1 in a sample.
Regarding instant claim 3, claim 32 of the reference application recites the particles comprise cells, Plouffe outlines the method in [Figure 3A], wherein the depicted cells are considered to correspond to live or dead cells, and the method of Ma is carried out on a homogenate that includes cellular debris [page 3, top].
Regarding instant claims 4 and 35, the limitation of “the concentration of cell nuclei in a fraction is increased” is interpreted to correspond to the increase in targeted cell nuclei compared to the sample before the separation step. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to an increase in the concentration of cell nuclei by at least 10% (corresponding to instant claim 4) and 50% (corresponding to instant claim 35) from the original sample.
Regarding instant claims 5 and 36, Ma discloses the modified INTACT method described in the rejection of instant claim 1 above, wherein a nuclear envelope fusion protein was used to isolated target nuclei using anti-GFP antibodies against GFP coupled to magnetic beads [p 2, para 1]. As this combined method of the reference application, Plouffe and Ma only isolates nuclei, it is considered to correspond to the reduction of non-nuclei particles of 1% (corresponding to instant claim 5) and 10% (corresponding to instant claim 36) compared to the original sample.
Regarding instant claim 7, Ma discloses the method adapted from the INTACT method described above which is carried out in Arabidopsis thaliana [p 1, para 2], which is understood as a plant. As the INTACT method developed for plants, one of skill in the art would be able to carry out the modified INTACT method of Ma in a plant cell.
Regarding instant claims 8 and 37-38, Ma discloses the method of nuclei isolation carried out on neuronal cell types within the adult brain of Drosophila which implicitly involve genetically modifying the cell types to contain the nuclear envelope fusion protein comprising GFP [p 2, para 1], and therefore corresponds to the isolation of nuclei from brain cells (corresponding to instant claim 37) and from gene-edited cells (corresponding to instant claims 8 and 38).
Regarding instant claim 12, in view of the indefiniteness of the instant claim, and for the sake of compact prosecution, the instant claim is being examined under the interpretation that the limitation of “the yield of nuclei in the first recovered sample is at least about 50%...of the total nuclei from the loaded sample” corresponds to the increase in targeted cell nuclei after separation compared to the loaded sample before separation. Therefore, Plouffe outlines the method in [Figures 3A and 3D] which indicates complete separation of labeled from non-labeled samples, and is therefore considered to correspond to the yield of nuclei being at least 50%.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 6 is newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 62 of co-pending Application No. 19/203107 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Nagata.
The instant rejection is newly stated as a result of the filing of the reference application.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite the limitations of integrity of cell nuclei.
Nagata relates to the isolation of intact nuclei of high purity [title], and discloses comparisons of nuclear isolation methods using different speeds of centrifugation [abstract].
Regarding instant claim 6, Nagata discloses that moderate centrifugal force (MCF) yielded higher purity of nuclei, high nuclei number per gram, and higher RNA per gram of sample when compared to high centrifugal force (HCF) [Table 1]. Nagata further discloses that isolated nuclei contained better membrane integrity with MCF than with HCF [p 182, col 1, para 2].
While Nagata does not disclose the % difference in integrity between centrifugal and non-centrifugal isolation methods recited in the instant claim, Nagata identifies centrifugal force as a result effective variable, which is a variable that achieves a recognized result according to MPEP 2144.05.II.B. In view of the disclosure of Nagata, one of skill in the art would expect that reducing centrifugal force would improve nuclei integrity, and therefore carrying out the combined method of the reference application, Plouffe and Ma which lacks centrifugation would result in increased nuclei integrity compared to a method with centrifugation. Furthermore, as the instant claim does not recite any specific method of isolation comprising centrifugation, one of skill in the art would be able to modify the method of Nagata by increasing the centrifugal speed, thereby decreasing nuclei integrity, in order to achieve the recited difference in nuclei integrity, as Nagata establishes the result effective variable of centrifugal force that effects the result of nuclei integrity, and therefore the % difference in integrity when comparing nuclei isolation methods lacking and methods comprising centrifugation.
In view of Nagata, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Plouffe and Ma by comparing membrane integrity to a modified method of Nagata to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Plouffe and Ma by comparing to a modified method of Nagata, because Nagata discloses the result effective variable of centrifugal force wherein higher centrifugal force results in lower nuclei integrity. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Nagata relate to methods to isolate cell nuclei from samples.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-32 newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 62 of co-pending Application No. 19/203107 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Shen.
The instant rejection is newly stated as a result of the filing of the reference application.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite a paramagnetic material that comprises Gd.
Shen relates to label-free cell separation using a tunable magnetophoretic repulsion force [title].
Regarding instant claim 29, Shen discloses the difference in magnetic forces acting on different sized cells is enhanced by adjusting the magnetic susceptibility of the surrounding medium, which depends on the concentration of paramagnetic salts, such as biocompatible gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) [abstract].
In view of Shen, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of the reference application, Plouffe and Ma by using the Gd-DTPA of Shen to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the magnetic beads of Plouffe and the Gd-DTPA of Shen are both paramagnetic compounds, and as such both are capable of being incorporated into magnetic-based separation methods such as those described by Plouffe and Ma. Thus it would have been obvious to one of ordinary skill in the art to replace the magnetic beads of Plouffe with the Gd-DTPA of Shen, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because Plouffe, Ma and Shen related discuss methods to separate biological materials by magnetic means.
Regarding instant claim 30, the Gd-DTPA of Shen [abstract] is understood to be a gadolinium chelate.
Regarding instant claims 31-32, Shen discloses solutions of Gd-DTPA with concentrations ranging 0 to 80 mM [p 3077, col, 2, para 2]. According to MPEP 2144.05.I, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 33-34 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 62 of co-pending Application No. 19/203107 in view of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 above, and further in view of Paul.
The instant rejection is newly stated as a result of the filing of the reference application.
The claims of the reference application and disclosures of Plouffe and Ma as applied to claims 1-5, 7-8, 12 and 35-38 are discussed above. The claims of the reference application do not recite the strength of a magnetic field.
Paul relates to cell separation techniques using high gradient magnetic fields [title], and discloses the magnetic isolation of cells containing hemoglobin without damaging cells or causing hemolysis [abstract] to utilize advantages of magnetic separation over techniques involving specific gravity [p 273, para 1] which is interpreted as techniques involving centrifugation.
Regarding instant claims 33-34, Paul discloses that applying magnetic field to samples with a strength above 0.5 Tesla corresponds to a separation of target cells that is proportional to the applied magnetic field at all flow rates, and also indicates the use of magnetic field strengths ranging from ~0.3 Tesla to 1.4 Tesla [p 276, para 4; and Figure 2].
In view of Paul, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Plouffe and Ma by applying the magnetic field strengths of Paul to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Plouffe and Ma by applying the magnetic field strengths of Paul, because Paul discloses magnetic isolation of cells has an advantage over techniques involving specific gravity as the magnetic isolation does not damage cells, and additionally shows a range of magnetic field strengths capable of separating cells based on their magnetic properties. One of ordinary skill in the art would have had a reasonable expectation of success because Plouffe and Paul relate to methods of isolating cells based on magnetic properties.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks: beginning on page 17 of Applicant’s response to nonstatutory double patenting rejections and page 1 of Applicant’s Declaration under 37 CFR 1.130; Applicant in summary contends co-pending Applicant 17/938825 is not prior art in view of an exception under 35 USC 102(b)(2)(C).
Applicants remarks and Declaration are fully considered and found not convincing. As Applicant’s Declaration under 37 CFR 1.130 to establish common assignment is directed to a prior art exception under 35 USC 102(b)(2)(C), it is not applicable to double patenting rejections. According to MPEP 710.01(I), the showing that a disclosure is not prior art under 35 USC 102(a) will make the disclosure unavailable to be applied in a rejection under either 35 USC 102(a) or 35 USC 103. The U.S. patents or U.S. patent application publications may continue to be applied under the judicially created doctrine of nonstatutory double patenting, or under statutory double patenting. Furthermore, MPEP 717.02(a).B states once common ownership is established, the subject matter disclosed in Patent A may not be used in a rejection under 35 U.S.C. 102 or 35 U.S.C. 103 against the claims of Application X. Patent A, however, could still be used as the basis for a double patenting rejection, if appropriate.
Therefore the provisional nonstatutory double patenting rejections of record are maintained or newly stated as set forth in the section above.
Conclusion
Status of the Application:
Claims 1-38 are pending.
Claims 9-11 and 13-28 are withdrawn.
Claims 1-8, 12 and 29-38 are rejected.
No claim is in condition for allowance.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656