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 .
Status of the Claims
Claims 1-19 are pending in the application and under consideration. Claims 1, 4, 17, and 19 have been amended. All previously set forth 112(b) rejections have been overcome and subsequently withdrawn herein.
Response to Arguments
Applicant's arguments filed November 14th, 2025 have been fully considered but they are not persuasive.
Regarding the rejection of claim 1, while the amended claim limitation is seen to overcome the prior presented rejection, in light of the teachings of Mitchell (WIPO Publication 2018/237081) the newly added limitation is seen to have been obvious to one of ordinary skill in the art (see below rejection of claim 1).
Regarding the rejection of claim 17, the amended claim language is not seen to overcome the previous rejection utilizing the disclosure of Braun. Claim 17 is currently drawn toward an apparatus rather than a method and as such limitations regarding the function or use of a device hold very little patentable weight outside of any structure that the limitation provides to the device. The limitation of the subject having a cf-DNA level of 50 ng/mL is not seen to provide any structure to the device and instead is drawn solely to when the device is to be used to treat a patient. As such this additional limitation hold very little patentable weight and is not seen to be sufficient to overcome the prior rejection with Braun (see below rejection of claim 17).
All other arguments presented lack any further substantive arguments outside of a general statement of disagreeing with the examiners rejection and as such are seen to be addressed by the above addressal of the arguments pertaining to claims 1 and 17.
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.
Claim 17 is 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 17 recites the limitation "the subject" in line 2. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination “the subject” is being interpreted to mean a subject that is receiving mechanical support from the mechanical support system or circuit, with support for this interpretation found in the method claim of claim 1.
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.
Claim(s) 17-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Braun et al. 2019 (see attached NPL reference “Limitation of Circulating cfDNA Under the Use of a Cytokine Elimination Adsorber (CytoSorbTM ) in Cardiac Surgery”).
Regarding claim 17, Braun discloses a mechanical support system or circuit that comprises a mechanical support device and a filter that reduces cell-free DNA (Objectives: patients undergoing cardiac surgery requiring CPB while using a CytoSorbTM cytokine absorber) and the mechanical support system being utilized on a patient for cfDNA elimination (Conclusion: CfDNA elimination using a CytoSorbTM adsorber has an immediate effect of reducing release of proinflammatory cytokines).
Braun does not expressly disclose the subject having a total cf-DNA level of over 50 ng/mL.
However, the limitations of “has a total cf-DNA level of over 50 ng/mL” is considered functional language as this limitation is describing the use of the device to treat a subject who has a total cf-DNA level of over 50 ng/mL as described by applicants’ specification on Page 9 Lines 1-5. While features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function, because apparatus claims cover what a device is, not what a device does (Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990)). Thus, if a prior art structure is capable of performing the intended use as recited the claim, then it meets the claim. In the instant case, the device of Braun discloses all the structure as claimed, and is further used to eliminate cfDNA from a subject. As such, it is capable of performing the functions as claimed (i.e. it is capable of being used to treat a subject with a total cf-DNA level of over 50 ng/mL).
Regarding claim 18, Braun discloses the method of claim 17. Braun further discloses the mechanical support device comprises a cardiopulmonary bypass device (Objectives: cardiopulmonary bypass).
Regarding claim 19, Braun discloses the method of claim 17. Braun further discloses the filter comprises CYTOSORB (Objectives: CytoSorbTM cytokine adsorber).
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.
Claim(s) 1-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Braun et al. 2019 (see attached NPL reference “Limitation of Circulating cfDNA Under the Use of a Cytokine Elimination Adsorber (CytoSorbTM) in Cardiac Surgery”) in view of Mitchell et al. (WIPO Publication 2018/237081).
Regarding claim 1, Braun discloses a method of treating a subject in need of mechanical support, the method comprising inhibiting the amount of cf-DNA in the subject (Conclusion: CfDNA elimination using a CytoSorbTM adsorber has an immediate effect of reducing release of proinflammatory cytokines).
Braun does not expressly disclose the subject having a total cf-DNA level over 50 ng/mL.
However, Mitchell, in the same field of endeavor of cf-DNA patient level determination, teaches providing a treatment to a subject exhibiting an amount of total cf-DNA equal to 8 ng/mL or greater as patients with this amount of cf-DNA or greater are seen to have a greater risk of complications including cardiac arrest (Page 20 lines 20-27 an amount equal to or greater than 8 or 9 ng/mL may be indicative of cardiac arrest).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Braun to have treated a subject having a total cf-DNA level over 50 ng/mL, as Mitchell teaches that subjects with 8 ng/mL or greater have a greater risk of complications including cardiac arrest, and since it has been held that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists”. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In the instant case, Braun in view of Mitchell would not operate differently with the claimed range as Mitchell is disclosed to operate with subjects having 8 ng/mL or greater which would include any levels over 50 ng/mL and the ability of the device to reduce cf-DNA is not limited by the level of cf-DNA present. Furthermore, applicant places no criticality on the ranged claimed, indicating simply that 50 ng/mL indicates an increased likelihood of death, cardiac arrest, or mechanical circulatory support with 25 ng/mL indicating longer hospital length of stay, and levels over 10 ng/mL predicted presence of infections (Page 7 lines 1-14 of applicant’s specification), showing that a subject is treated to other thresholds below the greater than 50 ng/mL threshold, and as such not shown to be critical to the treatment of the patient. As such it would have been obvious to one of ordinary skill in the art before the effective filing date to have treated a subject having a total cf-DNA level of over 50 ng/mL as this lies inside the range disclosed by the prior art and one would have treated a patient with 50 ng/mL total cf-DNA utilizing.
Regarding claim 2, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the subject is treated using mechanical support that comprises a filter that reduces the level of cf-DNA in the subject (CytoSorbTM adsorber).
Regarding claim 3, Braun in view of Mitchell suggest the method of claim 2. Braun further discloses the mechanical support comprises a cardiopulmonary bypass device (Objectives: using cardiopulmonary bypass).
Regarding claim 4, Braun in view of Mitchell suggest the method of claim 2. Braun further discloses the filter comprises an extracorporeal cytokine absorber (Conclusion: CytoSorbTM adsorber).
Regarding claim 5, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the subject being treated by administration of a cf-DNA inhibitor to the subject (Methods: CytoSorbTM adsorber administered to on-pump group, Conclusion: cfDNA eliminated using CytoSorbTM adsorber and thus inhibited from further action within the patients’ blood streams).
Regarding claim 6, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the method further comprises administering an additional therapy or treatment to the subject (Administration of Cardiopulmonary bypass to patient).
Regarding claim 7, Braun in view of Mitchell suggest the method of claim 6. Braun further discloses the additional therapy or treatment is any one of the therapies or treatments provided herein (Cardiopulmonary bypass treatment).
Regarding claim 8, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the subject is any one of the subjects described herein (subject in need of Cardiopulmonary bypass treatment).
Regarding claim 9, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the method further comprises determining an amount of cf-DNA in one or more samples from the subject (Results: both on-pump groups had significant 1.5-fold increase of cfDNA, levels of cfDNA quantified using Pico Green Staining).
Regarding claim 10, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the method further comprises comparing the amount of cf-DNA to a threshold (Results: compares to normal cfDNA levels, showed a significant earlier normalization of cfDNA levels) and at least one prior amount of cf-DNA (Results 1.5-fold increase of cfDNA compared with baseline).
Regarding claim 11, Braun in view of Mitchell suggest the method of claim 10. Braun further discloses the threshold is any one of the thresholds provided herein (Results compares to normal cfDNA levels).
Regarding claim 12, Braun in view of Mitchell suggest the method of claim 1. Braun further discloses the subject is one with, such as one who was determined to have, a level of cf-DNA greater than any one of the thresholds provided herein (Results: both on-pump groups had a significant 1.5 fold increase and on-pump CytosorbTM group showed a significant earlier normalization of cfDNA levels).
Regarding claims 13 and 14, Braun in view of Mitchell suggest the method of claim 9. Braun does not expressly disclose the amount of cf-DNA being determined or obtained using an amplification-based quantification assay wherein the amplification-based quantification assay is quantitative real-time PCR (qRT-PCR) or digital PCR, as Braun discloses obtaining the amount of cf-DNA through Pico-green fluorescence.
However, Mitchell, in the same field of endeavor of cf-DNA patient level determination, further teaches the amount of cf-DNA being determined or obtained using an amplification-based quantification assay wherein the amplification-based quantification assay is quantitative real-time PCR (qRT-PCR) (Page 23 lines 12-31 amplification-based quantification assay, such as quantitative PCR; Page 27 lines 27-33 Quantitative PCR including real-time PCR).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the Pico-green assay of Braun that performs the function of quantifying the amount of cf-DNA of a patient for the quantitative real-time PCR assay of Mitchell since these elements perform the same function of quantifying the concentration of plasma free-cell DNA of a patient sample. Simply substituting one cell-free DNA quantifying means for another would yield the predictable result of allowing a(n) amount of cell-free DNA of a patient to be quantified for analysis. See MPEP 2143.
Regarding claim 15, Braun in view of Mitchell suggests the method of claim 9. Braun further discloses the level of cf-DNA is determined in the subject daily (Methods: collected at 1 hour and 24 hours resulting in a daily determination).
Regarding claim 16, Braun in view of Mitchell suggests the method of claim 1. Braun further discloses the mechanical support and filter are part of a system that is used on the subject (Objectives: patients undergoing cardiac surgery requiring CPB while using a CytoSorbTM cytokine adsorber).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 PETER DANIEL SMITH whose telephone number is (571)272-8564. The examiner can normally be reached Monday - Friday 7:30am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sarah Al-Hashimi can be reached at 571-272-7159. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER DANIEL SMITH/Examiner, Art Unit 3781
/JESSICA ARBLE/Primary Examiner, Art Unit 3781