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8, 9, 12, 14, 17, 23, 42, 43, 44 and 51-62 are pending in this application, Claims 23 and 42-44 are acknowledged as withdrawn, Claims 8, 9, 12, 14, 17 and 51-62 were examined on their merits.
With this New Non-Final Rejection, the Finality of the prior action mailed 02/03/2026 is withdrawn in view of the New Rejections herein.
Response to Amendment
The Declaration under 37 CFR § 1.130(a) filed on 07/16/2026 is sufficient to overcome the rejection of claims 8, 9, 12, 14, 17 and 51-62 based on Brodie et al. (US 2022/0323957 A1).
Withdrawn Objections/Rejections
The objection to the Drawings because only that which is old is illustrated is withdrawn in view of the removal of Brodie et al. (US 2022/0323957 A1) as prior art.
The objection to the Specification because of the improper use of Trademarks has been withdrawn due to the Applicant’s amendments to the Specification filed 01/02/2026.
The rejection of Claims 8, 9, 17, 55, 60, 61 and 62 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2007/0114181 A1), both of record, has been withdrawn in view of the removal of Brodie et al. (US 2022/0323957 A1) as prior art.
The rejection of Claims 8, 9, 12, 14, 17, 55, 60, 61 and 62 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), and further in view of Levner et al. (US 2015/0005188 A1), all of record, has been withdrawn in view of the removal of Brodie et al. (US 2022/0323957 A1) as prior art.
The rejection of Claims 8, 9, 12, 14, 17, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 and 62 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, and further in view of Ogawa et al. (2021), cited in the IDS, has been withdrawn in view of the removal of Brodie et al. (US 2022/0323957 A1) as prior art.
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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 9, 12, 14, 17 and 51-62 are rejected 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. Claim 8 recites, “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”. It is unclear if it is the sample or the sample medium which comprises the paramagnetic compound or ferrofluid; and isolation particles.
Claim 8 recites, “…to affect a separation of the target subcellular component from other components in the sample”. It is unclear what “other components in the sample” are being referred to. Is it solely the contaminating species, paramagnetic compound/ferrofluid and isolation particles? Or other unspecified components, such as a buffer or medium.
Claim 8 recites, “…collecting at least one fraction of the separated sample comprising the target subcellular component without further centrifugation”. It is unclear how any collection can take place as there is no flow or movement required in the sample. Further, it is unclear if the phrase ”without further centrifugation” implies that a prior step of centrifugation has taken place or not.
Claim 8 recites, “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”. It is unclear how any movement can take place as there is no flow or movement required in the sample.
Further, there is no “direction” or selection thereof indicated in the prior steps of the claim. For purposes of examination, the Examiner has construed the limitation as being met with any movement in any direction. Claims 9, 12, 14, 17 and 51-62 are rejected as being dependent upon rejected Claim 8 and for failing to rectify the indefiniteness thereof.
Claim 9 recites, “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”. It is unclear how any movement can take place as there is no flow or movement required in the sample. Further, there is no “direction” or selection thereof indicated in the prior steps of the claim.
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.
Claims 8 and 9 are rejected under 35 U.S.C. § 103 as being unpatentable over Andersen et al. (2017) in view of Frenea-Robin et al. (01/14/2022).
Andersen et al. teaches loading a sample comprising a target subcellular component (membrane bound antigen CD3 or CD35), and contaminating species (non-T cell peripheral blood mononuclear cells or non-CD35 expressing red blood cells) (Pg. 3564, Column 1, Paragraphs 2.2-2.3);
and a medium comprising a paramagnetic compound (gadolinium) and antibody coated beads/isolation particles into a separation channel (capillary tube) and subjecting the sample to a magnetic force with two magnets to separate the membrane bound antigen target from the other non-antigen expressing cells (Pgs. 3463-3464, Column 2, Paragraph 2.4 and 2.6 and Pg. 3464, Fig. 1C);
wherein the isolation particles form a complex with the target antigen expressing cells which inhibits the movement of the target antigen expressing cells toward ambient gravitational force (e.g. chosen direction) relative to the movement of the non-target antigen expressing cells (Pg. 3466, Fig. 2 and Pg. 3468, Fig. 4), and reading on Claims 8 and 9.
The teachings of Andersen et al. were discussed above.
Andersen et al. did not teach a method wherein the isolation particles complex with the non-desired contaminating species or wherein at least one fraction of the separated sample comprising the target component is collected, as required by Claim 8.
Frenea-Robin et al. teaches wherein target components (cells) may be labeled with antibodies for positive selection (labeled cells are retained in the isolated fraction due to magnetic attraction) or negative selection wherein unwanted component (cells) are labeled leaving the wanted component (cells) fraction untouched and collected for downstream use (Pg. 9, last two lines and Pg. 10, Lines 1-4 and Fig. 4) wherein in cases where the antibody-magnetic bead conjugate may cause unwanted intracellular signaling or cell activation negative selection is preferred (Pg. 10, Lines 10-12).
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 positive selection of target subcellular components by antibody-bead magnetic levitation of Andersen et al. to use the negative selection method of Frenea-Robin et al. to label and remove unwanted components and collecting the desired target subcellular components because both methods of positive and negative selection using antibody-beads and magnetism were known in the art and could have been substituted for the other. See the MPEP citing KSR at 2143, I., B. Those of ordinary skill in the art would have been motivated to make this modification based on artisan preference and because Frenea-Robin teaches negative selection is preferred in certain situations. There would have been a reasonable expectation of success in making this modification because both references are reasonably drawn to the same field of endeavor, immunomagnetic separation of desired components.
Claims 8, 9, 12, 14, 17 and 62 are rejected under 35 U.S.C. § 103 as being unpatentable over Andersen et al. (2017) in view of Frenea-Robin et al. (01/14/2022), as applied to Claims 8 and 9 above, and further in view of Deal et al. (2010) as evidenced by Shan et al. (2014).
The teachings of Andersen et al. and Frenea-Robin et al. were discussed above.
Neither reference taught the target component is cell nuclei, as required by Claim 62;
wherein the particles are from about 1-10 microns in size, as required by Claim 12;
wherein the isolation particles are streptavidin coated polystyrene beads, as required by Claim 14;
wherein the sample comprises from about 50-10,000,000 cell nuclei, as required by Claim 17.
Deal et al. teaches a method wherein cell nuclei are contacted with magnetic beads coated with streptavidin and isolated using magnetic attraction (Pg. 58, Fig. 2) and wherein the sample can contain at least 1x105 (Pg. 59, Procedure);
wherein the beads are M-280 streptavidin (coated) DYNABEADS™ (Pg. 59, Column 1, Line 8).
Shan et al. evidences that DYNABEADS™ are polystyrene based microbeads (Pg. 138, Column 2, Lines 8-10).
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 negative selection of non-target components by antibody-bead magnetic levitation of Andersen et al. and Frenea-Robin et al. to isolate cell nuclei and utilize streptavidin coated magnetic microbeads as taught by Deal et al. by negative selection of non-target components because both Andersen and Deal teach that immunomagnetic separation can be used to isolate target cell components and Frenea-Robin teaches that both positive and negative selection using affinity beads and magnetism were known in the art and could have been substituted for the other. See the MPEP citing KSR at 2143, I., B. Those of ordinary skill in the art would have been motivated to make this modification in order to isolate desired cell nuclei and because Frenea-Robin teaches negative selection is preferred in certain situations. 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, immunomagnetic separation of desired components.
With regard to Claim 12, Andersen et al. teaches the beads have a diameter of 10 µm (Pg. 6465, Paragraph 3.1).
Claims 8, 9, 12, 14, 17, 51, 52, 53, 54 and 62 are rejected under 35 U.S.C. § 103 as being unpatentable over Andersen et al. (2017) in view of Frenea-Robin et al. (01/14/2022), and Deal et al. (2010) as evidenced by Shan et al. (2014), as applied to Claims 8, 9, 12, 14, 17 and 62 above, and further in view of Ogawa et al. (2021)
The teachings of Andersen et al., Frenea-Robin et al. and Deal et al. were discussed above.
None of the above references taught wherein the sample further comprises wheat germ agglutinin (WGA) in a nuclei isolating buffer, as required by Claims 51 and 52;
or wherein the nuclei isolating buffer comprises WGA and buffer, as required by Claims 53 and 54.
Ogawa et al. teaches contacting lysed cells with WGA, PBS and protease inhibitors (Pg. 17, 2nd Paragraph) and that WGA supplementation concentrated and preserved small nuclear proteins in the nucleus of cells with permeabilized plasma membranes (Pg. 8, 2nd paragraph).
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 negative selection of non-target components from a cell nuclei containing sample by affinity microbead magnetic levitation of Andersen et al., Frenea-Robin et al. and Deal et al. to include an nuclei isolating buffer comprising WGA as taught by Ogawa et al. because this would allow the isolation of small nuclear proteins in the cell nuclear fraction. Those of ordinary skill in the art would have been motivated to make this modification in order to isolate the cell nuclei and associated small nuclear proteins, if so desired. There would have been a reasonable expectation of success in making this modification because at least Deal et al. teaches the isolation of cell nuclei and Ogawa et al. teaches that nuclei isolation with WGA beneficially preserves small nuclear proteins.
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 unpatentable over Andersen et al. (2017) in view of Frenea-Robin et al. (01/14/2022), Deal et al. (2010) as evidenced by Shan et al. (2014), and Ogawa et al. (2021), as applied to Claims 8, 9, 12, 14, 17, 51, 52, 53, 54 and 62 above, and further in view of Knowlton et al. (2017).
The teachings of Andersen et al., Frenea-Robin et al., Deal et al. and Ogawa et al. were discussed above.
None of the above references taught wherein the sample is caused to flow along the separation channel, as required by Claims 55-61.
Knowlton et al. teaches a method of magnetic levitation wherein a separated cell sample comprising paramagnetic media is caused to flow along the separation channel (Pg. 2, Fig. 2).
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 negative selection of non-target components from a cell nuclei containing sample by affinity microbead magnetic levitation of Andersen et al., Frenea-Robin et al., Deal et al. and Ogawa et al. to cause the sample to flow along the separation channel as taught by Knowlton et al. because this would allow for the visualization and separation of the desired cell nuclei. Those of ordinary skill in the art would have been motivated to make this modification in order to visualize and isolate the cell nuclei and associated small nuclear proteins, if so desired. There would have been a reasonable expectation of success in making this modification because at least Andersen et al. teaches magnetic levitation of a sample in a static separation channel and Knowlton et al. teaches that magnetic levitation may be performed by flowing the sample through the separation channel.
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 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, 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 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 04/01/2026, with respect to the above withdrawn objections/rejections have been fully considered and are persuasive. However, upon further consideration, a new ground(s) of rejection is made in view of Andersen et al. (2017) in view of Frenea-Robin et al. (01/14/2022).
With regard to the obviousness-type double patenting rejection the Applicant argues that the ‘278 application is in pre-exam and will be subject to a claim amendment (Remarks, Pg. 4, Lines 21-24).
This is not found to be persuasive as the Examiner notes that no amendment has been submitted in the ‘278 application. Therefore the rejection remains in effect.
No claims are allowed.
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 04/14/2026
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