DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 9, 2026, has been entered.
Response to Amendment
The amendments to the claims filed June 9, 2026, incorporate the after final amendment filed April 13, 2026 (which previously had not been entered) and further amendments. However, the amendments fail to include all markings to indicate changes that have been made relative to the immediate prior version of the claims (claims filed August 27, 2025) and claim 19 has the wrong status identifier. As indicated in MPEP 714(II)(C), all claims being currently amended must be presented with markings to indicate the changes that have been made relative to the immediate prior version. Moreover, the status identifier of claim 19 should be ‘New.’
Claims 3 and 11 are cancelled. Claim 19 is new.
Claims 1, 2, 4-10, and 12-19 are pending. Claims 12-15 and 18 are withdrawn.
Claims 1, 2, 4-10, 16, 17, and 19 are examined on the merits.
Notice Re: Prior Art Available Under Pre-AIA and AIA
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 4, 5, 7, 8, 10, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal (US 2010/0068781. Listed on IDS filed 11/11/22) in view of Kemp (WO 2018/085817).
Rajagopal discloses methods for mechanical lysis, fracturing, crushing and compressing of objects such as biological samples (paragraph [0007]). The method of lysing a biological sample comprises placing the biological sample and at least one permanent magnet (directed to the claimed ‘at least one magnetic body’) inside a lysis tube, and generating a magnetic field which accelerates the at least one permanent magnet towards the biological sample for a time and under conditions sufficient to cause the biological sample to be lysed (claim 10 of Rajagopal). The magnetic field is produced by one or two electromagnets 60 (paragraph [0031] discussing Figure 1). The electromagnet is an arrangement made from a coil or wire which acts as a magnet when an electric current passes through it (paragraph [paragraph [0030]). Since an electric current passes through the electromagnet(s) of the invention of Rajagopal, then it is directed to an electric conductor.
Through the movement of the least one permanent magnet (the claimed ‘at least one magnetic body’) toward the biological sample, then the at least one permanent magnet collides with at least one molecule of the biological sample. Thus Rajagopal teaches a method comprising (a) colliding at least one magnetic body (at least one permanent magnet) with said at least one molecule under influence of a magnetic field generated by an electric conductor (the electromagnet(s)).
In lysing a biological sample, such as by lysing cells in a biological sample (paragraphs [0024]-[0025]), it would have been obvious to the person of ordinary skill in the art that at least one covalent bond is cleaved in at least one molecule of the biological sample which collides with the at least one permanent magnet. This would have been obvious in view of Kemp.
In particular, Kemp discloses bead beating for lysing cells, in which beads are agitated with enough force and frequency to lyses cells (paragraph [0063). Kemp states that cell rupture takes place when the kinetic energy of the colliding beads exceeds the elastic energy stored in the cell (paragraph [0063]). The acceleration of the at least one permanent magnet towards the biological sample to cause lysis of Rajagopal is directed to bead beating. Therefore, kinetic energy of the colliding permanent magnet(s) must have been applied to the cells of the biological sample of Rajagopal in order to exceed the elastic energy stored in the cells so that the cells are lysed.
Further still, it would have been obvious to the person of ordinary skill in the art that the transferred kinetic energy is sufficient to cleave at least one covalent bond that is inherently present in molecules of the biological sample, wherein the covalent bond cleavage occurs within at least one molecule of the cells of the biological sample, thereby resulting in fragmentation of the at least one molecule. Moreover, even though Rajagopal in view of Kemp does not recognize that at least one covalent bond is cleaved in at least one molecule, thereby resulting in fragmentation of the least one molecule, since Rajagopal in view of Kemp renders obvious step (a) of instant claim 1, then the claimed effects (the colliding/triggering transferring an amount of energy to at least one molecule sufficient to cleave at least one covalent bond in the at least one molecule, wherein the covalent bond cleavage occurs within the molecule, thereby resulting in fragmentation of the molecule) would have necessarily occurred.
Furthermore, Rajagopal also renders obvious the embodiment of instant claim 1 in which (b) (‘triggering collision of at least one non-magnetic particle…’) is performed. In particular, the method of Rajagopal can further comprise providing a plurality of lysis aids together with the biological sample inside the lysis tube (claim 11 of Rajagopal). The term “lysis aid” is used to indicate a particle that is suitable to aid in causing lysis of the biological sample (paragraph [0036]). As shown in Figure 1, the plurality of lysis aids 50 come into physical contact with the biological sample 40 during lysis (paragraph [0036]). The lysis aids 50 can be non-magnetic (paragraph [0036]). When performing the method of Rajagopal, the permanent magnets 30 can be moved by reversal of the magnetic field direction (paragraph [0037]). This movement forces the permanent magnets 30 into the lysis aids 50 with a considerable amount of force, and this force causes the biological sample 40 (e.g. biological cell) to shear against the lysis aids 50 (paragraph [0037]). This is directed to (b) of instant claim 1 of triggering collision of at least one non-magnetic particle (the lysis aids 50) with at least one molecule of the biological sample by moving at least one magnetic body (the permanent magnets 30) under influence of a magnetic field generated by an electric conductor (the electromagnets 60). For the same reasons as discussed above in view of Kemp, and since the references render obvious step (b) of instant claim 1, then the claimed effects would have necessarily occurred, i.e., the triggering transfers an amount of energy (kinetic energy) to the at least one molecule sufficient to cleave at least one covalent bond, wherein the covalent bond cleavage occurs within the molecule, thereby resulting in fragmentation of the molecule.
Therefore, Rajagopal in view of Kemp renders obvious instant claim 1.
Regarding instant claim 2, the reversal of the magnetic field direction (paragraph [0037]) is directed to a fluctuating magnetic field. In reversing the magnetic field direction, then the permanent magnets 30 (directed to the claimed ‘at least one magnetic body’) performs a fluctuating motion. Thus instant claim 2 is rendered obvious.
Regarding instant claim 4, the lysis tube of Rajagopal is directed to a ‘reactor.’ Also, the biological sample can be a liquid phase solution of cells (paragraph [0025]). Example 1 of Rajagopal performs their method by providing an aliquot of yeast cells suspended in phosphate buffered saline in a lysis tube (paragraph [0049]). Thus instant claim 4 is rendered obvious.
Regarding instant claim 5, the lysis tube is directed to a ‘reactor with a closed bottom,’ and in performing the method in the lysis tube in which there is not a continuous stream of the biological sample or other materials into the lysis tube, then the method rendered obvious by Rajagopal in view of Kemp is performed in batch mode. Thus instant claim 5 is rendered obvious.
Regarding instant claim 7, since the permanent magnets (claimed ‘at least one magnetic body’) are moved within the lysis tube around the center of the lysis tube (paragraph [0037]), then the dimensions of said at least one magnetic body (the permanent magnets) and said reactor (the lysis tube) are such that said at least one magnetic body moves freely about an average position (the center of the lysis tube). Thus instant claim 7 is rendered obvious.
Regarding instant claims 8 and 17, the walls/membrane of a cell (as the biological sample being lysed) inherently comprise macromolecules or a chain molecule, such as proteins which comprise at least two building blocks (amino acids). Thus instant claims 8 and 17 (amino acids) are rendered obvious.
Regarding instant claim 10, the cells being lysed by the method rendered obvious by Rajagopal in view of Kemp inherently comprise proteins. As discussed above with respect to instant claim 4, cells in the Rajagopal invention are provided in a solution or suspension in the lysis tube. In lysing cells, at least one covalent bond of the proteins (directed to ‘at least one molecule’) on the cell wall or membrane is cleaved. Thus (e) of instant claim 10 is met, thereby rendering obvious the claim.
Regarding instant claim 16, Rajagopal discloses reversing the magnetic field direction so as to move the permanent magnets 30 toward the center of the lysis tube 10 (paragraph [0037]). See also Figure 1. This is directed to the permanent magnets 30 moving freely around or along at least two axes of translation motion. Thus instant claim 16 is rendered obvious.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal and Kemp as applied to claims 1, 2, 4, 5, 7, 8, 10, 16, and 17 above, and further in view of Belgrader (US 2013/0157274. Previously cited).
As discussed above, Rajagopal in view of Kemp renders obvious claims 1, 2, 4, 5, 7, 8, 10, 16, and 17. Rajagopal in view of Kemp differs from claim 9 in that they do not expressly disclose bringing at least one of an enzyme, a chemical, and a catalyst in contact with the at least one molecule (of the biological sample) to cleave the at least one covalent bond of said at least one molecule.
Belgrader discloses a method in the same field as Rajagopal in that Belgrader discloses a method of lysing cells, virus particles, and spores, the method comprising stirring cells with a magnetic stir element in a container in the presence of a plurality of cell lysis beads (paragraph [0004]). The cell lysis beads are of materials that are not magnetic, e.g. polymer beads, glass beads (paragraph [0004]). A magnetic field is applied to the container such that the magnetic field causes the magnetic stir element to collide with the plurality of cell lysis beads and produces a cell lysate (paragraph [0007]). In certain embodiments, lysing of particular cell types can be facilitated by adding additives to the cell suspension prior to and/or during the stirring step (paragraph [0039]). Examples of additives include enzymes, detergents, surfactants and other chemicals such as bases and acids (paragraph [0039]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to include an enzyme, a detergent, a surfactant, a base, or an acid in the lysis tube when performing the method rendered obvious by Rajagopal in view of Kemp in which cells are the biological sample being lysed. One of ordinary skill in the art would have been motivated to do this because enzymes and those chemicals facilitate the lysing of cells, as pointed out by Belgrader. There would have been a reasonable expectation of successfully lysing cells by this modification of the method rendered obvious by Rajagopal and Kemp because these additives were added to a cell suspension in a method of lysing cells involving a magnetic body (the magnetic stir element of Belgrader, directed to the permanent magnet of Rajagopal), non-magnetic particles (the non-magnetic cell lysis beads of Belgrader, directed to the lysis aids of Rajagopal), and application of a magnetic field. In this method rendered obvious by Rajagopal in view of Kemp and further in view of Belgrader, then an enzyme or a chemical is in contact with the molecules where the lysing occurs on the cells (claimed ‘at least one molecule’) to cleave at least one covalent bond in said molecules. Thus instant claim 9 (an enzyme or a chemical) is rendered obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 4, 5, 7, 8, 10, 16, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-15, 20, and 21 of copending Application No. 17/924,113 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the fragmenting of a protein, a polypeptide, and a peptide molecule of the claims of `113 is directed to cleaving at least one covalent bond in the protein/polypeptide/peptide molecule. The electromagnet comprising at least one coil of claim 1 of `113 is directed to an electric conductor. Additionally, the dependent claims of `113, when combined, meet limitations of the claimed invention. In particular, in applying the limitations of claim 4 of `113 to claim 1 of `113 and the other claims of `113d, then the claimed limitations of (a) colliding at least one magnetic body with the at least one molecule under influence of a magnetic field generated by an electric conductor (the electromagnet of the claims of `113), and (b) triggering collision of at least one non-magnetic particle with at least one molecule by moving at least one magnetic body under the influence of the magnetic field generated by an electric conductor (the electromagnet of the claims of `113). The claims of `113 differ from the instant claims in that the claims of `113 do not recite that the colliding or triggering transfers an amount of energy to the at least one molecule sufficient to cleave at least one covalent bond, wherein the covalent bond cleavage occurs within the molecule, thereby resulting in the fragmentation of the molecule. However, the collision of a particle with a molecule necessarily transfers kinetic energy to the molecule. Moreover, it would have been obvious that this transfer of energy is sufficient to cleave at least one covalent bond since fragmentation of at least one molecule is recited in the claims of `113. Thus each of claims 1, 3, 5-15, 20, and 21 of `113 in view of claim 4 of `113, render obvious instant claim 1.
Regarding instant claim 2, claim 1 of `113 recites that the at least one magnetic body performs a fluctuating or oscillating motion triggered by a fluctuating or oscillating magnetic field, meeting a limitation of instant claim 2. Therefore, claim 1 of `113 in view of claim 4 of `113 renders obvious instant claim 2.
Regarding instant claim 4, claim 5 of `113 meets a limitation of instant claim 4, and claim 21 of `113 recites a reactor for the practice of the invention. It would have been obvious to apply the limitations of claims 5 and 21 of `113 to claim 1 of `113. Therefore, claim 1 of `113 in view of claims 4, 5, and 21 of `113 renders obvious instant claim 4.
Regarding instant claim 5, claim 5 of `113 recites the embodiment of the sample comprising a solution or suspension of the molecule. Claim 21 of `113 recites a reactor, vessel, or tube. Each of these are directed to a reactor with a closed bottom, and it would have been obvious to use each as these as a batch mode as it would have been an obvious matter of selecting from known modes for use of a reactor. Therefore, claim 1 of `113 in view of claims 5 and 21 of `113 renders obvious instant claim 5.
Further regarding instant claims 7 and 16, claim 1 of `113 recites the free movement of the magnetic body being centered on at least three, at least four, at least five, or all six axes of translation and rotational motion. The center of the axes is directed to the claimed ‘average position.’ Therefore, claim 1 of `113 in view of claim 4, 5, and 21 of `113 renders obvious instant claims 7 and 16.
Further regarding instant claim 10, claim 1 of `113 recites that the at least one molecule is selected from a protein, a polypeptide, and a peptide molecule. This meets (e) of instant claim 10. Thus claim 1 of `113 in view of claims 4, 5, and 21 of `113 renders obvious instant claim 10.
Regarding instant claims 8 and 17, claim 1 of `113 recites that the at least one molecule is selected from a protein, a polypeptide, and a peptide molecule. Each of these are directed to a macromolecule or chain molecule comprising at least two amino acids (building blocks). Thus claim 1 of `113 in view of claim 4 of `113 renders obvious instant claims 8 and 17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments, filed June 9, 2026, with respect to the rejection under 35 U.S.C. 102(a)(1) and 102(a)(2) of claims 1-5, 7, 8, 10, 16, and 17 as being anticipated by Rajagopal, and the rejection under 35 U.S.C. 103 of claim 9 as being unpatentable over Rajagopal in view of Belgrader have been fully considered and are persuasive. In particular, the rejections have been overcome by the amendments to the claims. Therefore, these rejections have been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of the newly cited reference Kemp, as necessitated by the amendments to the claims. Moreover, as pointed out above, since Rajagopal renders obvious steps (a) and (b) of instant claim 1, then the claimed effects (cleaving at least one covalent bond in at least one molecule, wherein the colliding or triggering transfers an amount of energy to at least one molecule sufficient to cleave at least one covalent bond, wherein the covalent bond cleavage occurs within the molecule, thereby resulting in fragmentation of the molecule) necessarily occurs. Regarding Rajagopal, Applicant’s arguments are unpersuasive to the extent they are directed to the new grounds of rejection. The Examiner has considered Exhibits A and B filed on June 9, 2026. Paragraph [0024] of Rajagopal is cited by Applicant for it’s teaching of cell lysis being useful for the analysis of DNA, RNA, proteins or lipids. Therefore, Applicant concludes that the purpose of Rajagopal is to release intact biomolecules such as DNA, RNA, proteins, and lipids from cells. Further still, Exhibit A (Islam) is cited for its discussion of cell lysis for the release of inter-cellular materials such as DNA, RNA, protein or organelles from a cell, and bead collision with cells for breaking open the cell membrane and release the intracellular components by shear force. However, the fact that the cell lysis is used for the purpose of release of intracellular components does not mean that covalent bonds are not broken within molecules occurring in cell walls or cell membranes. Also, Exhibit B (Alberts) is not persuasive for supporting Applicant’s assertion that disruption of cell membranes since cells have different cells walls/membranes (for instance, gram positive bacteria versus gram negative bacteria versus plant cells versus mammalian cells).
Applicant argues that since the purpose of cell lysis in Rajagopal is to release nucleic acids, proteins and other intracellular components for downstream analysis, then any conditions that would intentionally cleave covalent bonds within biomolecules would undermine this objective, because fragmentation of DNA or proteins would interfere with subsequent analytical techniques. However, this does not mean that any covalent bond in biomolecules within the walls/membranes of cells cannot be broken. Therefore, the Examiner disagrees that Rajagopal teaches away from the claimed invention.
Regarding the nonstatutory double patenting rejection, Applicant requests that the rejection be held in abeyance until otherwise allowable subject matter has been identified in the present case. However, only compliance with objections or requirement as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated.
Conclusion
Claims 1, 2, 4, 5, 7-10, 16, and 17 are rejected.
Claim 6 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 19 is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSAN EMILY FERNANDEZ whose telephone number is (571)272-3444. The examiner can normally be reached 10:30am - 7pm.
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Sef
/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
