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 .
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 6,8,10-11,17-22,24, and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (US 2018/0266951) and further in view of Gross et al. (US 2011/0034370).
Regarding claim 1 Spero discloses a method for isolating a cell free DNA (cfDNA) from a biological sample comprising the cfDNA, the method comprising: (i) contacting the biological sample with a histone, wherein the histone forms a complex with the cfDNA; (ii) separating the complex obtained in step (i) from the biological sample, and (iii) releasing the cfDNA from the complex separated in step (ii). (See Spero Abstract [0205]-[0212] wherein cfDNA is isolated from a whole blood sample by binding to and forming a complex with a histone within a device and separating the complex from the sample by flowing the remaining sample out of the device. The cfDNA is then released from the complex by using protease.)
Spero does not specifically disclose using a linker histone to bind the cfDNA.
Gross discloses linker histones which may be utilized for a variety of purposes including binding with DNA.(See Gross Abstract [0023]-[0024], and [0039] wherein histones including linker histones are known to bind DNA.)
It would have been obvious to one of ordinary skill in the art at the time of invention to provide the linker histones of Gross in the device of Spero because such linker histones are known to be efficiently produced and to bind DNA and represent effective linkers for binding cfDNA as is required by the binding molecules of Spero.
Regarding claim 6 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the linker histone is immobilized on a solid support.(See Spero [0209] wherein the histone is bound to a solid support)
Regarding claim 8 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the linker histone is bound to a magnetic particle. (See Spero wherein the surface attached structures are magnetic particles.)
Regarding claims 10-11 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the biological sample is a blood sample. (See Spero [0209] wherein a whole blood sample is provided as the biological sample.)
Regarding claim 17 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the linker histone is a mammalian somatic linker histone. (See Gross [0039]-[0040] wherein the linker histone is a human linker histone, i.e. a mammalian somatic linker histone.)
Regarding claims 18-21 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the linker histone H1 is a human H1.0 linker histone. (See Gross [0039]-[0040] wherein the linker histone H1 is a human H1.0 or H1.3 linker histone.)
Regarding claim 22 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the linker histone comprises an amino acid sequence which is at least 70% identical to the sequence SEQ ID NO: 1 or SEQ ID NO: 2. (See Gross SEQ ID NO: 9 which is at least 70% identical to sequence SEQ ID NO: 1.)
Regarding claim 24 modified Spero discloses all the claim limitations as set forth above as well as the method wherein releasing the cfDNA comprises contacting the complex with a protease. (See Spero [0211] wherein releasing is done using protease.)
Regarding claim 35 modified Spero discloses all the claim limitations as set forth above as well as the method wherein the separating step (ii) comprises one or more of centrifugation, sedimentation or filtration.(See Spero [0210] wherein size exclusion, i.e. filtration, and settling, are used to separate cfDNA from other sample portions.)
Allowable Subject Matter
Claim 23 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.
Applicant's arguments filed 7/23/2025 have been fully considered but they are not persuasive.
Applicant argues that Spero does not suggest histones to bind cfDNA but instead uses anti-histone antibodies and that Spero does not suggest the use of linker histones to bind cfDNA.
The examiner notes that while Spero may in fact use anti-histone antibodies such antibodies bind to histone which is in turn bound to the cfDNA, i.e. in other words the cfDNA must be bound to the histone in order to bind to the anti-histone antibody.
While Spero gives such an anti-histone antibody as a specific example of a cfDNA binding molecule it does not limit the disclosure to such a specific example. Thus while Spero does not disclose using linker histones as binding molecules the examiner provided an additional reference and rational to disclose such features and make up for such deficiencies in Spero.
Applicant also argues that one would not be led by Spero to look to Gross and that even if combined do not give preference to linker Histones. It is noted that Spero notes that the binding molecules used in the present invention may be any molecules which effectively bind to the target molecule, i.e. cfDNA in this case, and that removal of such cfDNA from a biological sample is used to allow treatments for conditions such as cancer.
Gross discloses a system wherein Histones including H1 linker histone are used to remove, i.e. scavenge, cfDNA from a biological sample to enable cancer treatment. Thus one of ordinary skill in the art at the time of invention would have been motivated to utilize such linker histones as the binding molecules in Spero in order to effectively bind cfDNA for cancer treatment and because such molecules represent specific cfDNA binding molecules which are required by Spero.
Applicant further argues that they have demonstrated superior and unexpected results. The examiner notes that while applicant may provide one example in which the described method provides a superior result over another known method such a demonstration on superiority is not commensurate in scope with the claimed invention nor does it directly reflect the material taught in the cited prior art. As such the demonstration of superior results is not persuasive.
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 JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONATHAN M HURST/ Primary Examiner, Art Unit 1799