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 .
The amendment filed August 27, 2025, has been received and entered.
Claim 11 is canceled.
Claims 1-10 and 12-18 are pending. Claims 12-15 and 18 are withdrawn.
Claims 1-10, 16, and 17 are examined on the merits.
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 7 and 16 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 7 is indefinite because it is unclear what is meant by “an average position.” It is not a term in the art, and the specification does not define the term. Since claim 7 is indefinite, then its dependent claim, claim 16, is rendered indefinite. Thus, claims 7 and 16 are rejected under 35 U.S.C. 112(b).
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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 7, 8, 10, 16, and 17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Rajagopal (US 2010/0068781. Listed on IDS filed 11/11/22).
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 place 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. In lysing a biological sample, such as by lysing cells in a biological sample (paragraphs [0024]-[0025]), then at least one covalent bond is inherently cleaved in at least one molecule of the biological sample which collides with the at least one permanent magnet. Thus Rajagopal anticipates instant claim 1 by disclosing a method of cleaving at least one covalent bond in at least one molecule (as present in the biological sample), wherein said method comprises (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)).
Furthermore, Rajagopal also anticipates 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), wherein at least one covalent bond of the at least one molecule is cleaved through lysis.
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 anticipated.
Regarding instant claim 3, colliding the permanent magnets (claimed ‘at least one magnetic body’) with the at least one molecule of the biological sample (where the biological sample, e.g. cell, is lysed) inherently transfers kinetic energy. That kinetic energy inherently cleaves the at least one covalent bond of the at least one molecule of the biological sample. Thus instant claim 3 is anticipated.
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 anticipated.
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 of Rajagopal is performed in batch mode. Thus instant claim 5 is anticipated.
Regarding instant claim 7, the Examiner is interpreting ‘an average position’ as any position. 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 anticipated.
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 anticipated.
Regarding instant claim 10, the cells being lysed by the method of Rajagopal 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 anticipating 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 anticipated.
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.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal in view of Belgrader (US 2013/0157274. Previously cited).
As discussed above, Rajagopal anticipates claims 1-5, 7, 8, 10, 16, and 17. Rajagopal differs from claim 9 in that Rajagopal does 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 of Rajagopal 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 is successfully lysing cells by this modification of Rajagopal 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 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, 8, 10, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 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 is directed to cleaving at least one covalent bond in the protein/polypeptide/peptide molecule. Additionally, the dependent claims of `113, when combined, meet limitations of the claimed invention. In particular, in applying the limitations of claim 2 of `113 (the electromagnet is directed to the claimed ‘electric conductor’) and the limitations of claim 4 of `113, then instant claim 1 is rendered obvious. Thus each of claims 1, 3, 5-15, 20, and 21 of `113, in view of claims 2 and 4 of `113, render obvious instant claim 1. Claim 2 of `113 in view of claim 4 of `113 renders 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 claims 2 and 4 of `113 renders obvious instant claim 2.
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 claims 2 and 4 of `113 renders obvious instant claims 8 and 17.
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 2 and 4 of `113 renders obvious instant claim 10.
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 August 27, 2025, with respect to the objection to the specification, and the rejections under 35 U.S.C. 112(b) of claims 3 and 6 have been fully considered and are persuasive. In particular, the amendment to the specification has overcome the objection. The rejections under 35 U.S.C. 112(b) have been overcome by the amendments to claims 3 and 6. Therefore, the objection and these rejections have been withdrawn.
However, Applicant’s arguments are unpersuasive with respect to the rejection under 35 U.S.C. 112(b) of claim 7, 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.
Regarding the rejection under 35 U.S.C. 112(b) of claim 7, Applicant asserts that the meaning of “an average position” would be understood by a person of ordinary skill in the art. Additionally, Applicant asserts that the present application as filed defines “an average position” at least at page 9, lines 1-8. However, the cited passage speaks of the motion being generally about an average position which is located within an enclosure or container, and states “said average position may be somewhere in the middle of said reactor.” However, these teachings do not constitute a definition of “an average position,” and instead provides an example of an average position (somewhere in the middle of the reactor).
Regarding the rejection under 35 U.S.C. 102, Applicant asserts that Rajagopal fails to disclose each and every element recited in independent claim 1. In particular, Applicant argues that Rajagopal fails to disclose “cleaving at least one covalent bond in at least one molecule.” Applicant points out that Rajagopal is silent regarding cleaving covalent bonds. The Examiner agrees that the reference does not specifically teach cleaving covalent bonds. However, the fact that Rajagopal does not refer to cleaving covalent bonds does not mean that it does not inherently occur. Moreover, Applicant asserts that a proper reading of Rajagopal reveals that cleaving of covalent bonds is not only not inherent but is also avoided. Applicant then asserts that the method of Rajagopal is designed to trigger cell lysis while avoiding cleavage of covalent bonds to avoid damage to covalent bonds in target molecules, citing, paragraph [0005] of the reference, for example, which describes thermal lysis. However, the fact that thermal lysis causes cellular protein denaturation and is not ideal for assaying relatively rare DNA, RNA or protein targets does not signify that cleaving covalent bonds is undesirable for the method of Rajagopal. Bischof (Ann. N.Y. Acad. Sci. 2005. 1066: 12-33) discusses heat-induced denaturation of proteins (abstract), pointing out that protein denaturation is a process in which a protein is transformed from an ordered to a less-ordered state due to the rearrangement of hydrogen bonding without any change to covalent bonds (page 16, first paragraph). Since thermal lysis does not involve changing covalent bonds, then the teachings regarding thermal lysis in paragraph [0005] of Rajagopal (distinct from the mechanical lysis taught by Rajagopal) does not provide any indication that cleavage of covalent bonds should be avoided. Therefore, Rajagopal, including its paragraph [0005], does not have any teaching of avoiding cleavage of covalent bonds.
Additionally, Applicant cites MPEP 2163 and MPEP 2112 for passages regarding inherency. Applicant argues that the Office action has not provided a basis to reasonably support the determination that “cleaving at least one covalent bond in at least one molecule” is inherent in Rajagopal for at least the reasons set forth in the above arguments. The Examiner respectfully disagrees – as set forth in the rejection, in lysing a biological sample, such as by lysing cells in a biological sample (paragraphs [0024]-[0025]), then at least one covalent bond is inherently cleaved in at least one molecule of the biological sample which collides with the at least one permanent magnet.
Regarding the rejection under 35 U.S.C. 102(a)(1) and 102(a)(2) of claim 10 as being anticipated by Rajagopal, Applicant argues against the basis of the rejection, specifically the statement in the rejection that in lysing cells, at least one covalent bond of the proteins (directed to ‘at least one molecule’) on the cell membrane or membrane is cleaved. Applicant argues that this assertion contrasts with a skilled person’s common general knowledge and understanding of the specification, and a skilled person would consider non-covalent interactions important for lysing cells, since these interactions are conventionally understood to hold the membrane together. However, Applicant has not provided any evidence to support their assertions regarding the skilled person’s common general knowledge and the importance of non-covalent interactions for lysing cells, nor has Applicant cited any passage from the specification to support their argument.
Because Applicant’s arguments against Rajagopal are unpersuasive, then the Examiner is unpersuaded by Applicant’s argument against the rejection under 35 U.S.C. 103 of claim 9 over Rajagopal in view of Belgrader. Applicant asserts that Belgrader fails to disclose or suggest “cleaving at least one covalent bond in at least one molecule,” but the Examiner maintains that this limitation is inherently met by Rajagopal.
Regarding the provisional non-statutory double patenting rejection over claims 1-15 and 20 of co-pending Application No. 17/924,113, Applicant defers filing a Terminal Disclaimer until indication of otherwise allowable claims.
Conclusion
Claims 1-5, 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.
THIS ACTION IS MADE FINAL. 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.
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Sef
/SUSAN E. FERNANDEZ/Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651