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 claims
Claims 1-3 and 5-12 as amended on 7/27/2026 pending and under examination in the instant office action.
Claim Rejections - 35 USC § 112
Indefinite
Claims 1-3 and 5-12 as amended 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 1 as amended is indefinite with regard to characterization of a patient and of a woman (healthy woman or control) because differences between claim-recited term “cell-free DNA” for a patient with inflammation and pain associated to endometriosis and claim-recited term “free DNA” for women without endometriosis are not certain when applied to different groups of people. Is there a different between “cell-free DNA” and “free DNA”? Specification does not provide definitions.
For examination purpose, these terms are/have been regarded as equivalents.
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.
Claims 1-4 as amended remain/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/134403 (Boettcher et al) in view of Zachariah et al (IDS reference; Reproductive Biomedicine on line; 2009, Vol. 18, No. 3, pages 407-411).
The cited document WO 2018/134403 (Boettcher et al) discloses the use of enzyme DNase for treating tissue adhesion that occur during endometriosis (see abstract; see page 1, par. 2; see page 5, par. 2 last 2 lines). Thus, the cited documents teaches a method for treating endometriosis in a patient, comprising administering an effective dose of DNase to said patient. The enzyme DNase is a recombinant DNase (page 11, par. 2). The enzyme DNase is DNase I (page 5, last paragraph). The cited document recognizes that DNase I catalyzes decomposition of free DNA (page 5, last par.). But the cited document does not explicitly state that women with endometriosis have greater level of free DNA over women who do not have endometriosis.
However, it is well known in the art that women with endometriosis have greater level of free DNA over women who do not have endometriosis and that concentration of free DNA in plasma of patients is a biomarker for development of diagnosis of endometriosis; for example: see abstract of the reference by Zachariah et al.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to treat a women with endometriosis with DNase as taught by WO 2018/134403 (Boettcher et al) upon endometriosis diagnosis based on a level of free DNA because endometriosis diagnosis is associated with greater level of cell free DNA as compared to level of cell free DNA of women without endometriosis as taught/suggested evidenced by Zachariah.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1-5 as amended remain/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/134403 (Boettcher et al) and Zachariah et al (IDS reference; Reproductive Biomedicine on line; 2009, Vol. 18, No. 3, pages 407-411) as applied to claims 1-4 above, and further in view of Deraya et al (IOP publishing: Earth and Environmental Science 457 (2020) 0120079, pages 1-7).
The cited documents WO 2018/134403 (Boettcher et al) and Zachariah et al are relied upon as explained above.
In particular, the cited document WO 2018/134403 (Boettcher et al) teaches a method for treating endometriosis in a patient by administering an effective dose of DNase or DNase I. The cited document recognizes that DNase I catalyzes decomposition of free DNA (page 5, last par.). But the cited document does not explicitly disclose characterization of cell free DNA in patients with endometriosis is characterized by specific gene methylation profiles including methylation of gene such as FN1.
However, it is known in the art that there is a significant difference in methylation level of FN1 gene in cases of endometriosis over a normal condition; for example: see abstract of reference by Deraya.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed that cell free DNA of patients with endometriosis are characterized by specific methylation profiles including methylated gene such as FN1 (Deraya).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1-12 as amended remain/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/134403 (Boettcher et al) and Zachariah et al (IDS reference; Reproductive Biomedicine on line; 2009, Vol. 18, No. 3, pages 407-411) as applied to claims 1-4 above, and further in view of Deraya et al (IOP publishing: Earth and Environmental Science 457 (2020) 0120079, pages 1-7) as applied to claims 1-5 above, and further in view of WO 2014/020564 (Hazout et al).
The cited documents WO 2018/134403 (Boettcher et al), Zachariah et al and Deraya are relied upon as explained above.
In particular, the cited document WO 2018/134403 (Boettcher et al) teaches a method for treating endometriosis in a patient by administering an effective dose of DNase or DNase I. The cited document WO 2018/134403 (Boettcher et al) clearly recognizes that enzyme DNase I catalyzes decomposition of free DNA (page 5, last par.). The effective doses as taught by WO 2018/134403 are 2000 to 6000 U of the enzyme (page 17, last line), wherein the disclosed dose range covers the claim-recited dose. Further, the cited document WO 2018/134403 clearly teaches and suggests that specific amount and/or protocol of administering DNase enzyme depend on several factors, including body weights and severity of conditions of subject, and that those of skill in the art would obviously appreciate and optimize effective doses of DNase enzyme (page 17, par. 2).
Furthermore, the cited WO 2014/020564 (Hazout et al) teaches that enzyme DNase is administered intramuscularly (page 7, par. 3, last line); and it discloses dose 2500 UI of DNase twice a day for at least 7 days (page 7, last 3 lines) as intended to decrease high pathological levels of cell-free DNA (page 7, par. 4). It is known that woman with endometriosis are characterized by high pathological levels of cell-free DNA (Zachariah). The cited document WO 2018/134403 (Boettcher et al) clearly recognizes the therapeutic function of DNase I for decomposition of free DNA (page 5, last par.) in patients with endometriosis.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to modify specific amounts and/or protocol of administering enzyme DNase in the method of WO 2018/134403 (Boettcher et al) for treating endometriosis with a reasonable expectation of success because woman with endometriosis are characterized by high pathological levels of cell-free DNA (Zachariah), because enzyme DNase I catalyzes decomposition of free DNA as recognized by WO 2018/134403 (Boettcher et al) and because those of skill in the art would obviously appreciate and optimize effective doses of enzyme depending on several factors including severity of condition of patients with endometriosis as recognized by WO 2018/134403 (Boettcher et al).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed on 7/27/2026 have been fully considered but they are not all found persuasive.
The rejection of claims under 35 U.S.C. 102 (a) (1) as being anticipated by WO 2018/134403 (Boettcher et al) has been withdrawn because the cited document does not explicitly teach treating endometriotic patients with the use of cell free DNA for diagnosis of endometriosis and associated symptoms.
With regard to claim rejection under 35 U.S.C. 103 Applicants argue that WO 2018/134403 (Boettcher et al) does not explicitly teach treating endometriotic patients with DNase and is silent about treating inflammation and pain associated with endometriosis (response page 4).
This argument is not found persuasive because WO 2018/134403 (Boettcher et al) explicitly states that tissue adhesions occur in the course of inflammation during endometriosis (page 1, par. 2) and teaches administration of DNase for these conditions (page 2, par, 4). Thus, the patients under treatments are endometriotic patients, and these patients do have inflammation as stated therein. Clearly, adhesions in endometriotic patients would cause pain at the very least upon body moving and/or as result of pulling organs and tissue out of normal positions.
Applicant further argue (response page 5) that secondary references and Zachariah, in particular, do not remedy deficiencies of Boettcher.
This argument is not found persuasive because although Boettcher does not teach a specific diagnostic protocol for distinguishing between women with and without endometriosis, it is well known in the art that women with endometriosis have greater level of free DNA over women who do not have endometriosis and that concentration of free DNA in plasma of patients is a biomarker for development of diagnosis of endometriosis as clearly taught Zachariah.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to treat a women with endometriosis and adhesions resulted from endometriosis with DNase as taught by WO 2018/134403 (Boettcher et al) upon endometriosis diagnosis based on a level of free DNA because endometriosis is associated with greater level of cell free DNA as compared to level of cell free DNA of women without endometriosis as evidenced by Zachariah.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
No claims are allowed.
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.
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Vera Afremova
September 5, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653
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