DETAILED ACTION
The amendment filed on 11/03/2025 has been entered and fully considered. Claims 1-21 are pending. Claims 15 and 17-20 have been withdrawn from consideration. Claims 1-14 and 21 are considered on merits, of which claim 1 and 10 are amended, and Claim 21 is newly added.
Response to Amendment
In response to amendment, the examiner maintains rejection over the prior art established in the previous Office 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 .
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.
Claim 1-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-10 and 16-17 of copending Application No. 17/924,950 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the currently patented claims expressly recite the same subject matter, it would have been obvious to one of ordinary skill in the art at the time the invention was made to employ both device and methods, as recited in both sets of claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rajagopal et al. (US 2010/0068781) (Rajagopal).
Regarding claim 1, Rajagopal teaches a method of preparing a sample for an analytic procedure (abstract), said sample comprising at least one molecule selected from a protein, a polypeptide and a peptide molecule (par [0024]), and said method comprising:
(a) fragmenting said molecule using at least one moving magnetic body (30) to produce fragments of said molecule, wherein said at least one magnetic body performs a fluctuating or oscillating motion triggered by a fluctuating or oscillating magnetic field (60), wherein free movement of the magnetic body is centered on at least two, at least three, at least four, at least five, or all six axes of translational and rotational motion (Fig. 1, par [0032]).
By lysing cells in a biological sample (par [0024] [0025]), at least one covalent bond is inherently cleaved in at least one molecule of the biological sample which collides with the at least one moving magnet body.
The claim does not require free 6-dimentional motion, only “at least two axes,” which is a very broad requirement. Rajagopal’s system meets this breadth, as the magnets undergo:
translation along the tube axis
rotation/realignment in response to field reversals
This satisfies “at least two” axes.
Regarding claim 2, Rajagopal teaches that wherein said magnetic field is generated by an electric current and/ or an electromagnet (par [0031]).
Regarding claim 3, Rajagopal teaches that wherein:
(i) said fragmenting is a non-enzymatic and non-chemical process (par [0032]).
Regarding claim 4, Rajagopal teaches that wherein said magnetic body collides with said molecule; and/ or at least one non-magnetic particle (50) is present, wherein said motion of said magnetic body triggers collision of said at least one non-magnetic particle with said molecule (par [0036]).
Regarding claim 5, Rajagopal teaches that wherein said sample is of biological origin and comprises:
(i) a solution or suspension of said molecule (40) (Fig. 1, par [0025]);
(ii) a cell selected from a prokaryotic and a eukaryotic cell (par [0025]); and/or
(iv) tissue (par [0025]).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 6-7 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal et al. (US 2010/0068781) (Rajagopal).
Regarding claim 6, Rajagopal fairly suggests that the method further comprising:
(b) exposing said sample to heat, denaturing said sample, adding
detergent to said sample, and/ or adding a chaotropic agent to said sample (par [0005]).
wherein step (b) can be performed prior to or concomitantly with step (a).
Regarding claim 7, Rajagopal fairly suggests that the method further comprising:
(c) chemically modifying said molecule and/ or the fragments obtained from of said molecule (par [0004]).
Regarding claim 21, Rajagopal clearly shows that the dimension of the magnetic body in Fig. 2 is significantly smaller than the dimension of the magnetic body in Fig. 1.
Rajagopal teaches placing a magnetic body inside a reactor/tube and oscillating the body via an alternating magnetic field (par [0032] [0037], FIG. 2). For such oscillatory motion to occur, the magnetic body must be sufficiently smaller than the tube’s internal cross-section to permit back-and-forth movement.
Rajagopal further teaches that the size of the magnetic body and the size of the non-magnetic body may be varied to optimize lysis conditions for a specific organism or sample-type (par [0046]). This is extremely important because:
It shows explicit design flexibility for the magnet size.
It teaches that magnet dimensions are not fixed or restricted to a single geometry.
It identifies size variation as a design parameter for performance optimization.
It implies adjusting magnet size relative to tube clearance, bead size, and desired motion.
A POSITA would understand that for the permanent magnet to oscillate under the alternating magnetic field (par [0037]) and move freely within the tube, the magnet must have clearance relative to the tube interior. Selecting a magnet whose largest dimension is less than or equal to half of the tube’s smallest internal cross-section is nothing more than a predictable optimization of a parameter that the reference expressly identifies as variable. Such optimization would have been obvious to achieve the desired free oscillatory motion.
Claim(s) 8-9 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal et al. (US 2010/0068781) (Rajagopal) in view of Shin et al. (AB Sciex, 2013) (Shin).
Regarding claim 8 and 14, Rajagopal does not specifically teach that wherein said analytic procedure is mass spectrometry (MS). However, Shin teaches analysing protein or peptide with mass spectrometry (page 2, par 1). It would have been obvious to one of ordinary skill in the art to analyze the fragmented molecule by mass spectrometry, the result is predictable.
Regarding claim 9, Rajagopal does not specifically teach that wherein said chemically modifying said molecule and/ or the fragments of said molecule is selected from:
(ca) reducing a disulfide;
(cb) alkylating a thiol group such as a cysteine residue;
(cc) cross-linking; or
(cd) any combination of (ca), (cb) and (cc).
Shin teaches chemically modifying protein molecule and/ or the fragments of said molecule by
(ca) reducing a disulfide (page 1, par 3)
(cb) alkylating a thiol group such as a cysteine residue (page 1, par 3).
It would ahe been obvious to skill in the art to modify the protein molecule, in order to study the protein structure.
Claim(s) 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal et al. (US 2010/0068781) (Rajagopal) in view of Hughes et al. (Molecular Systems Biology, 2014) (Hughes).
Regarding claim 11, Rajagopal does not specifically teach that the method further comprising:
(d) cleaning and/ or enriching the obtained fragments.
However, Hughes teaches cleaning and/ or enriching the obtained fragments (page 3, par 1). It would ahe been obvious to skill in the art to clean and/or enrich the obtained fragments, in order to increase the sensitivity.
Regarding claim 12, Hughes also teaches
(e) labeling said molecule and/ or the fragments (page 3, par 1).
Regarding claim 13, Hughes teaches reacting a functional group of said molecule with a reagent capable of forming a conjugate with said functional group, wherein said reagent capable of forming a conjugate is a tag (TMT) which is detectable by mass spectrometry (page 3, par 1).
Allowable Subject Matter
Claim 10 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 and file terminal disclaimer.
The following is a statement of reasons for the indication of allowable subject matter: The prior art of record does not teach or fairly suggest adding at least one of an inert viscous liquid; a polyacrylamide gel; agarose gel; an aerogel; and a zeolith to said sample.
Response to Arguments
Applicant's arguments filed 11/03/2025 have been fully considered but they are not persuasive.
1. Rajagopal teaches the claimed fragmentation of a protein, polypeptide, or peptide molecule
Applicant asserts that Rajagopal is limited to “cell lysis” and does not teach fragmentation of proteins or peptides (Remarks, pp. 7–8).
This argument is not persuasive. Rajagopal discloses mechanical lysis, fracturing, crushing, and compressing of biological samples (Abstract; par [0007]) using moving permanent magnets accelerated by an oscillating magnetic field. Such repeated high-energy collisions inherently cause breakage of molecular structures, including covalent bonds within proteins, polypeptides, or peptides contained in the biological sample.
Rajagopal states that the biological sample includes proteins (par [0024]) and that lysis is performed by forcing permanent magnets through beads and sample material with “a considerable amount of force” (par [0037]).
Examiner notes that mechanical shearing of protein molecules is a well-known inherent result of bead-beating and magnetic-impact lysis, which rely on the same type of mechanical collisions as described in Rajagopal.
Accordingly, a skilled artisan would understand that the mechanical crushing and fracturing disclosed in Rajagopal necessarily fragments at least some proteins or peptides contained in the sample, even if the reference does not expressly state “covalent bond cleavage.” See MPEP 2112 (Inherency); In re Best, 562 F.2d 1252 (CCPA 1977) (“Where the claimed and prior art products are identical or substantially identical, the PTO can require an applicant to prove that the prior art products do not necessarily possess the characteristics of his claimed product.”).
Applicant’s argument that Rajagopal “teaches away” from protein fragmentation (Remarks, pp. 7–8) is not supported. The cited statements in par [0005] merely indicate that thermal lysis may denature proteins; they do not criticize, discourage, or teach away from mechanical lysis using moving magnetic bodies. Mechanical shearing is the central mechanism of Rajagopal.
Thus, the limitation “fragmenting said molecule using at least one moving magnetic body to produce fragments of said molecule” is expressly and inherently taught by Rajagopal.
2. Rajagopal teaches the claimed fluctuating / oscillating motion
Applicant does not dispute that Rajagopal teaches an oscillating AC-driven magnetic field producing oscillatory magnet motion (par [0037]). Rajagopal states:
“AC reverses direction … causing the permanent magnet to be alternately attracted and repulsed… Mechanical lysis is achieved through a repeated movement… back and forth within the lysis tube during a 60 Hz AC current.” (par [0037]).
This disclosure meets the requirement that: “said magnetic body performs a fluctuating or oscillating motion triggered by a fluctuating or oscillating magnetic field.”
3. Rajagopal teaches or renders inherent the claimed free movement along multiple translational or rotational axes
Applicant argues that Rajagopal’s magnet is “restricted to motion along an axis” (Remarks, p. 9) and therefore cannot meet the requirement of free movement "centered on at least two… axes."
This argument is not persuasive.
3.1 Even the single disclosed embodiment includes rotation and multidirectional repositioning
Although one embodiment shows constrained lateral movement, Rajagopal also discloses that magnet manipulation dimensionality, spacing, and geometry may be tailored (par [0046]); that magnet placement and field orientation can be used to “control the manipulation of magnetic particles” (par [0046]) and that the size of the magnetic body and the size of the non-magnetic body may be varied to optimize lysis conditions for a specific organism or sample-type (par [0046]).
Nothing in Rajagopal limits free motion to only one axis across all embodiments. The reference broadly teaches that magnet movement depends on design choices.
Further, the permanent magnetic body within a cylindrical tube inherently exhibit rotational degrees of freedom when the alternating magnetic field reverses, particularly when clearance exists, as shown in Figs. 1 and 2.
Thus, at least two axes of translational/rotational movement are inherently present.
3.2 Applicant’s claim uses an open “at least” formulation
The claim does not require free 6-dimentional motion, only “at least two axes,” which is a very broad requirement. Rajagopal’s system meets this breadth, as the magnets undergo:
translation along the tube axis
rotation/realignment in response to field reversals
This satisfies “at least two” axes.
4. Applicant’s “purpose” distinction is not persuasive
Applicant argues that Rajagopal is intended to preserve biomolecules for downstream assays (Remarks, pp. 7–8). However, the intended use or purpose of the prior art is irrelevant to anticipation so long as the structure or method performs the claimed steps. See MPEP 2111.02; In re Schreiber, 128 F.3d 1473 (Fed. Cir. 1997).
Rajagopal’s mechanical impact scheme is identical in structure and operation to Applicant’s claimed magnetic-driven fragmentation mechanism.
5. Overall conclusion
Applicant has not identified any claim element that is absent from the disclosure of Rajagopal. The arguments rely on distinctions in intended purpose and preferred modes of operation, which do not overcome anticipation.
The rejection under 35 U.S.C. §102(a)(1) is therefore maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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/XIAOYUN R XU, Ph.D./Primary Examiner, Art Unit 1797