DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 8, 9, 12, 14, 17, 23, 42-44 and 51-62 are pending in this application, Claims 23 and 42-44 are acknowledged as withdrawn, Claims 8, 9, 12, 14, 17 and 51-62 were examined on their merits.
Rejections Withdrawn
The rejection of Claims 8, 9, 12, 14, 17 and 51-61 under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to
particularly point out and distinctly claim the subject matter which the inventor or a joint
inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as
the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 01/02/2025.
The rejections of Claims 8, 12 and 14 for indefinite language has been withdrawn due to the Applicant’s amendments to the claims filed 01/02/2025.
The rejection of Claim 12 for containing trademark/trade names has been withdrawn due to the Applicant’s amendments to the claims filed 01/02/2025.
The rejection of Claim 52 for lacking antecedent basis has been withdrawn due to the Applicant’s amendments to the claims filed 01/02/2025.
Response to Declaration
The Declaration under 35 U.S.C. § 102(b)(2)(c) filed 01/02/2025 is sufficient to overcome the rejection of claims 8, 9, 12, 14, 17 and 51-61 based upon Lazaruk et al. (US 2023/0109713 A1).
The Declaration under 35 U.S.C. § 102(b)(2)(c) filed 01/02/2025 is insufficient to overcome the rejection of claims 8, 9, 12, 14, 17 and 51-61 based upon Brodie et al. (US 2022/0323957 A1) as set forth in the last Office action and below because: The reference qualifies as prior art under § 102(a)(1), and is “by another”, and cannot be excepted as prior art using a § 102(b)(2)(c) exclusion.
Drawings
Figures 1-8, 10-16, 18-23, 25 and 26 should be designated by a legend such as
-Prior Art-- because only that which is old is illustrated. See MPEP § 608.02(g).
Corrected drawings in compliance with 37 CFR 1.121(d) are required in reply to the
Office action to avoid abandonment of the application. The replacement sheet(s) should be labeled "Replacement Sheet" in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures.
If the changes are not accepted by the Examiner, the Applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the terms LEVICELL®, RNEASY® and QUANTSTUDIO® which are
trade names or marks used in commerce, has been noted in this application. The terms
should be accompanied by the generic terminology; furthermore the terms should be
capitalized wherever they appear or, where appropriate, include a proper symbol
indicating use in commerce such as TM, , SM , or ® following the term. 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.
Claim Interpretation
The Examiner notes that Claims 8, 9, 12, 14 and 52 all contain
"optional" limitations. The broadest, reasonable interpretation of an optional limitation is
that it is not required, therefore the claims have been construed thusly.
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.
Applicant has provided evidence in this file showing that the claimed invention and the subject matter disclosed in the prior art reference were owned by, or subject to an obligation of assignment to, the same entity as Brodie et al. (US 2022/0323957 A1) not later than the effective filing date of the claimed invention, or the subject matter disclosed in the prior art reference was developed and the claimed invention was made by, or on behalf of one or more parties to a joint research agreement in effect not later than the effective filing date of the claimed invention. However, although reference Brodie et al. (US 2022/0323957 A1) has been excepted as prior art under 35 U.S.C. § 102(a)(2), it is still applicable as prior art under 35 U.S.C. § 102(a)(1) that cannot be excepted under 35 U.S.C. 102(b)(2)(C).
Applicant may rely on the exception under 35 U.S.C. § 102(b)(1)(A) to overcome this rejection under 35 U.S.C. § 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. § 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. § 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
Claims 8, 9, 17, 55, 60, 61 and New Claim 62 are rejected under 35 U.S.C. § 103 as being unpatentable over Brodie et al. (US 2022/0323957 A1) in view of Li et al. (US
2007/0114181 A1), both of record.
Brodie et al. teaches a method of isolation of the subcellular component (cellular nuclei) comprising loading a sample comprising cell nuclei and a sample medium comprising a paramagnetic compound or ferrofluid into a separation channel;
flowing the sample into a processing/separation channel (Pg. 17, Paragraph
[0226]), and subjecting the 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 further centrifugation and;
optionally imaging the nuclei in the sample prior to, during, and/or after the
separation (Pg. 23, Claim 1), and reading on Claims 8 and 62.
With regard to Claim 17, Brodie et al. teaches wherein the sample comprises
from about 50 to about 10,000,000 cell nuclei; and/or wherein the concentration of cell
nuclei in a fraction is increased by at least 1.1:1 from the original sample; and/or
wherein the concentration of non-nuclei particles in the original sample is
decreased by at least about 1% in the fraction; and/or wherein the integrity of isolated
cell nuclei in a fraction from a sample is at least about 30% greater than the integrity of
cell nuclei isolated in a fraction from a sample by a method comprising centrifugation
(Pg. 4, Paragraphs [0033]-[0037]).
The teachings of Brodie et al. were discussed above.
Brodie et al. did not teach a method wherein the sample medium further
comprises isolation particles form a complex with one or more of the contaminating
species, or form a structure in the sample medium that interacts with one or more of the
contaminating species, in a manner that inhibits the movement of the one or more
contaminating species in a chosen direction relative to the movement of the target
subcellular component in the same direction, as required by Claim 8;
or wherein the particles form a complex with one or more of the contaminating
species, or form a structure in the sample medium that interacts with one or more of the
contaminating species, in a manner that inhibits the movement of the one or more
contaminating species in the direction of ambient gravitational force relative to the
movement of the target subcellular component in the same direction, as required by
Claim 9;
or wherein the sample comprising the target subcellular component, the
contaminating species, and a sample medium comprising: i) a paramagnetic compound
or ferrofluid; and ii) isolation particles (or beads), is caused to flow along the separation
channel, as required by Claims 55, 60 and 61.
Li et al. teaches a method of separating a contaminant from an untreated starting
material comprising: (a) contacting said starting material with an affinity moiety capable
of binding the contaminant to form a target comprising the affinity moiety bound to the
contaminant; (b) contacting the target of step (a) with a magnetic nanoparticle capable of binding the affinity moiety to form a magnetic target; and c) separating the magnetic target from said starting material, wherein the magnetic nanoparticle is bound to the affinity moiety prior to step (a) (Pg. 11, Claim 6).
Li et al. further teaches that the method may utilize either magnetic nanoparticles
or magnetic microbeads with a diameter of 2.8 µm (Pg. 6, Paragraph [0059]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Brodie et al. isolating cell
nuclei from a sample comprising cell nuclei using flowing magnetic levitation to further
include isolation particles, as taught by Li et al. in the sample medium comprising a
paramagnetic compound or ferrofluid because this would allow for the separation of the
desired subcellular component with the simultaneous removal of undesired
contaminants from the sample.
Those of ordinary skill in the art would have been motivated to make this modification in order to obtain an isolated fraction containing the cell nuclei which is also free of contaminants. There would have been a reasonable expectation of success because both references are drawn to the same field of endeavor, that is, the magnetic separation/removal of components from biological mixtures.
With regard to Claims 55, 60 and 61, it would have been obvious to those of
ordinary skill in the art before the effective filing date of the instant invention to modify
the method of Brodie et al. and Li et al. of separating desired components (cell nuclei) of
interest from non-desired components in a mixture using magnetic levitation and
magnetic isolation particles to flow the sample, the sample medium and the isolation
particles along the separation channel in order to simultaneously achieve separation of
desired components from undesired components and removal of contaminating components.
Those of ordinary skill in the art would have been motivated to make this
modification in order to achieve separation and isolation of desired components and
removal/separation of undesired components in one step. There would have been a
reasonable expectation of success because Brodie et al. teaches magnetic separation
of liquid suspended components in a flow channel and Li et al. teaches a liquid based
magnetic separation.
It would be inherent in the method of Li et al. that the magnetic nanoparticles
would inhibit the movement of the one or more contaminating species in a chosen
direction relative to the movement of the target subcellular component in the same
direction because the particles immobilize the contaminants in the direction of the
magnetic force while unbound components can flow freely in another direction, see Li et
al. (Fig. 2C).
Claims 8, 9, 12, 14, 17, 55, 60, 61 and 62 are rejected under 35 U.S.C. § 103 as
being unpatentable over Brodie et al. (US 2022/0323957 A1) in view of Li et al. (US
2007/0114181 A1), as applied to Claims 8, 9, 17, 55, 60, 61 and 62 above, and further in view of Levner et al. (US 2015/0005188 A1), all of record.
The teachings of Brodie et al. and Levner et al. were discussed above.
Neither reference taught a method wherein the isolation particles are from about
1-10 microns in size, and are streptavidin coated polystyrene particles, as required by
Claims 12 and 14.
Levner et al. teaches particles which may be from about 50nm to about 500 µm
(encompassing the claimed range of about 1-10 µm) which may be magnetic or
paramagnetic and polystyrene (Pg. 22, Paragraph [0194]); and which may be modified
by protein coating such as streptavidin (Pg. 22, Paragraph [0196]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Brodie et al. and Li et al. of
separating desired subcellular components of interest from non-desired components in
a mixture using magnetic levitation and magnetic isolation particles to use the particles
of Levner et al. because Li et al. does not specify the composition of the magnetic
particles and Levner et al. provides specific magnetic particles suitable for biological
applications. Those of ordinary skill in the art would have been motivated to make this
modification based on the availability of compounds and artisan preference. There
would have been a reasonable expectation of success in making this modification
because at least both Li and Levner are drawn to the same field of endeavor, that is,
magnetic particles and the use thereof.
Claims 8, 9, 12, 14, 17, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 and 62 are rejected under 35 U.S.C. § 103 as being obvious over Brodie et al. (US 2022/0323957 A1) in view of Li et al. (US 2007/0114181 A1), both of record, as applied to Claims 8, 9, 12, 14, 17, 55, 60, 61 and 62 above, and further in view of Ogawa et al. (2021), cited in the IDS.
The teachings of Brodie et al. and Li et al. were discussed above.
Neither Brodie et al. or Li et al. taught a method wherein the sample further
comprises a wheat germ agglutinin (WGA), as required by Claim 51;
wherein the sample is obtained by lysing intact cells with a nuclei isolating buffer
comprising WGA, as required by Claim 52;
wherein the WGA is present in an amount of from about 0.01-2mg/ml and the
nuclei isolating buffer comprises a buffer, as required by Claims 53 and 54.
Ogawa et al. teaches a method comprising contacting intact cells with a
composition comprising 100 µg/mL (or 0.1 mg/mL) of WGA to obtain a nuclear soluble
fraction (Pg. 17, Lines 11-22) and wherein the WGA solution comprises the buffers
Hepes-NAOH, potassium acetate, magnesium acetate and EGTA-NAOH (Pg. 15, Lines
28-32).
It would have been obvious to those of ordinary skill in the art to modify the
method of Brodie et al. and Li et al. of magnetically separating a desired/target
component of interest (cell nuclei) from undesired/non-target/contaminating components in a mixture, to use the method of Ogawa et al. to obtain the sample containing the
desired cell organelle and one or more non-desired components because Brodie et al.
does not indicate by what means their sample is obtained and Ogawa et al. provides a
specific means for obtaining a sample with the desired cell nuclei. Those of ordinary
skill in the art would have been motivated to make this modification in order to obtain
starting sample with the desired cell nuclei. There would have been a reasonable
expectation of success in making this modification because all of the references are
reasonably drawn to the same field of endeavor, that is, the separation of desired from
non-desired cellular components.
With regard to Claims 56, 57, 58 and 59, it would have been obvious to those of
ordinary skill in the art before the effective filing date of the instant invention to modify
the method of Brodie et al., Li et al. and Ogawa et al. of separating desired subcellular
components of interest (nuclei) from non-desired components in a mixture using magnetic levitation and magnetic isolation particles to flow the sample, the sample medium and the isolation particles along the separation channel in order to simultaneously achieve separation of desired components from undesired components and removal of contaminating components. Those of ordinary skill in the art would have been motivated to make this modification in order to achieve separation and isolation of desired components and removal/separation of undesired components in one step. There would have been a reasonable expectation of success because at least Brodie et al. teaches magnetic separation of liquid suspended components in a flow channel and Li et al. teaches a liquid based magnetic separation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees.
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 8, 9, 12, 14, 17 and 51-62 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 8, 9, 12, 13, 15 and 20 of copending Application No. 19/333,278 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application is drawn to: a method of isolation of a target subcellular component (cellular nuclei), from a sample comprising the target subcellular component and one or more contaminating species, comprising: loading a sample comprising the target subcellular component, the contaminating species, and a sample medium comprising: i) a paramagnetic compound or ferrofluid; and ii) isolation particles; into a separation channel along which the sample is optionally caused to
flow; subjecting the sample to a magnetic force with at least one magnet to affect a
separation of the target subcellular component from other components of the sample;
collecting at least one fraction of the separated sample comprising the target subcellular
component without further centrifugation and; optionally imaging the target subcellular
component in the sample prior to, during, and/or after the separation; wherein: a) the
isolation particles form a complex with one or more of the contaminating species, or
form a structure in the sample medium that interacts with one or more of the
contaminating species, in a manner that inhibits the movement of the one or more contaminating species in a chosen direction relative to the movement of the target subcellular component in the same direction; or b) the isolation particles form a complex with the one or more of the contaminating species, or form a structure in the sample medium that interacts with one or more of the contaminating species, in a manner to increase the movement of the one or more contaminating species in a chosen direction relative to the movement of the target subcellular component in the same direction; optionally wherein the target subcellular component (cell nuclei) is isolated from human cells, non-human animal cells, or plant cells.
This is made obvious by Claim 8 of the co-pending '278 application which is
drawn to: a method of isolation of a target subcellular component, e.g. cellular nuclei,
from a sample comprising the target subcellular component and one or more
contaminating species, comprising: loading a sample comprising the target subcellular
component, the contaminating species, and a sample medium comprising: i) a
paramagnetic compound or ferrofluid; and ii) isolation particles (or beads); into a well or
separation channel along which the sample is optionally caused to flow; subjecting the
sample to a magnetic force with at least one magnet to affect a separation of the target
subcellular component from other components of the sample; collecting at least one
fraction of the separated sample comprising the target subcellular component without
further centrifugation and; optionally imaging the target subcellular component in the
sample prior to, during, and/or after the separation; wherein the isolation particles are
from about 10 nanometers to about 15 microns in size; and wherein: a) the isolation
particles form a complex with one or more of the contaminating species, or form a structure in the sample medium that interacts with one or more of the contaminating species, in a manner that inhibits the movement of the one or more contaminating species in a chosen direction relative to the movement of the target subcellular component in the same direction; or b) the isolation particles form a complex
with the one or more of the contaminating species, or form a structure in the sample
medium that interacts with one or more of the contaminating species, in a manner to
increase the movement of the one or more contaminating species in a chosen direction
relative to the movement of the target subcellular component in the same direction.
Those of ordinary skill in the art would have recognized that the "comprising"
language of instant Claim 8 does not preclude the additional elements of Claim 8 of the
co-pending application, such as the limitation directed to the isolation particle size.
Instant Claims 9&55&60&61, 12, 14, 17 and 51-59 are made obvious by Claims
8, 9, 12&13, 15, 20, 1, 2 and 3 of the co-pending '278 application.
Response to Arguments
Applicant’s arguments, see Remarks, filed 01/02/2026, with respect to the above withdrawn rejections have been fully considered and are persuasive.
Applicant's remaining arguments filed 01/02/2026 have been fully considered but they are not persuasive.
The Applicant argues that the requirement that the Figures be designated as “Prior Art” is not necessary as neither of the cited references as prior art (Remarks, Pg. 18, Lines 9-15).
This is not found to be persuasive for the reasoning provided under the ‘Drawings’ heading above.
The Applicant argues that the amendments to the Specification address the objection to the Specification for improper use of Trademarks (Remarks, Pg. 18, Lines 17-19).
This is not found to be persuasive as the Examiner notes that no amendments to the Specification were filed with the Response.
The Applicant argues, citing the Declaration filed under 35 U.S.C. § 102(b)(2)(c) on 01/02/2025, that Brodie et al. (US 2022/0323957 A1) the publication of Application No. 17/938,825, is subject to an obligation of assignment to the present Applicant and is not prior art (Remarks, Pg. 19, Lines 25-30 and Pg. 20, Lines 1-2).
This is not found to be persuasive because, as discussed above, the Declaration under 35 U.S.C. § 102(b)(2)(c) filed 01/02/2025 is insufficient to overcome the rejection based on Brodie et al. (US 2022/0323957 A1) because the reference qualifies as prior art under § 102(a)(1), and is “by another”, and cannot be excepted as prior art using a § 102(b)(2)(c) exclusion.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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