U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`REMARKS
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`Please reconsider the application in View of the amendments presented herein and the
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`following remarks.
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`Disposition of the Claims
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`Claims l-12 are pending prior to the instant amendment. Claims l-4, 7 and 8 are herein
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`amended. New claims 13-17 are herein added.
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`No new matter has been added by way of amendment. Written support can be found
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`throughout the Specification as originally filed.
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`After entry of this amendment, claims l-l7 are pending and under examination, among
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`which claims 1, 7, 8, l3 and 17 are independent claims.
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`Specification
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`The Specification is objected to due to alleged informality in the Brief Description of the
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`Drawings in particular in regard to Figure 11.
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`Applicant has herein amended the Brief Description of the Drawings and enclosed a
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`Substitute Specification in both clean and marked versions.
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`Accordingly, reconsideration and withdrawal of the objection is respectfully requested.
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`Color Drawings
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`Applicant does not wish to have any color drawings appear in any patent that may issued
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`from the instant application.
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`Claim Rejection under 35 U.S.C. § 112
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`Claims 8-12 stand rejected as having improper dependency under 35 U.S.C. § 112, fourth
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`paragraph.
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`Without acquiescing to the rejection and in an effort to advance the examination of the
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`present application, Applicant has amended claim 8 which is now an independent claim.
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`Accordingly, reconsideration and withdrawal of the rejection is respectfully requested.
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`Claim Rejection under 35 U.S.C. § 101
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`Claims 1-7 stand rejected under 35 U.S.C. § 101 as being directed to patent ineligible
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`subject matter.
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`Without acquiescing to the rejection and in an effort to advance the examination of the
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`present application, Applicant has amended claim 1.
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`Amended claim 1 recites a method of diagnosing endometriosis in a mammal comprising
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`a step of: determining the circulating levels of glycodelin in a plasma sample from the mammal by
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`contacting the sample with a glycodelin antibody raised in a host animal. Support for the use of
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`glycodelin alone as a biomarker is found in the originally filed specification, for example, in
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`paragraph [0111], and support for the use of a glycodelin antibody is found, for example, in
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`paragraphs [0043] and [0089].
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`Claim 7 has similarly been amended.
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`Applicant respectfully submits that claims 1 and 7 as amended define patent-eligible
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`statutory subject matter.
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`The USPTO recently re-emphasized the importance of proper evaluation of patent
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`eligibility issues in patent examination by stating that “unless careful consideration is given to the
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`particular contours of subject matter eligibility (35 U.S.C. §101), it could ‘swallow all of patent
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`law.’ Alice Corp. v. CLSBank International, 573 US. _, _, 134 S.Ct. 2347, 2352 (2014) (citing
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`Mayo Collaborative Servs. V. Prometheus Labs, Inc, 566 US. 66, 71, 132 S.Ct. 1289, 1293-1294
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`(2012))” (USPTO, Changes in Examination Procedure Pertaining to Subject Matter Eligibility,
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`April 19, 2018.)
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`The first step of the eligibility analysis is to ask: Is the claim to a process, machine,
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`manufacture or composition of matter? Applicant respectfully submits that each of claims 1 and
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`7 is directed to a “process” as provided in 35 U.S.C. §101.
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`The second step of the eligibility analysis is to ask: Whether a claim is directed to a judicial
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`exception, i.e., is the claim directed to a law of nature, a natural phenomenon (product of nature)
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`or an abstract idea?
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`Applicant respectfully submits that amended claims 1 and 7 are not directed to a judicial
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`exception. A claim is directed to a judicial exception when a law of nature, a natural phenomenon,
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`or an abstract idea is recited in the claim. In contrast, amended claims 1 and 7 each recites a non-
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`natural process that involves manipulating non-naturally occurring materials.
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`Even if, arguendo, amended claim 1 and/or claim 7 were to be interpreted to recite a
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`judicial exception, Applicant respectfully submits that each claim as a whole (e.g., reciting
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`additional elements in an ordered combination) amounts to significantly more than the exception.
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`Specifically, circulating levels of glycodelin are determined in a plasma sample using a
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`non-naturally occurring antibody raised in a host animal. Circulating levels of glycodelin so
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`determined are compared to a pre-determined level associated with endometriosis.
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`In regard to the conclusory finding that the “correlation between the expression of each of
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`BDNF, glycodelin [], and ZAG [] and biological disorders is well-understood,
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`routine,
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`conventional activity,” Applicant respectfully points out that the Federal Circuit recently drew a
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`distinction between what is well-understood, routine, conventional, and what is simply known in
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`the prior art, cautioning that the mere fact that something is disclosed in a piece of prior art does
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`not mean it was a well-understood, routine, conventional activity or element. Berkheimer v. HP
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`Inc, 881 F.3d 1360, 1369 (Fed. Cir. 2018.) The question of whether additional elements represent
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`well-understood, routine, conventional activity is distinct from patentability over the prior art
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`under 35 U.S.C. §§ 102 and 103. An element or a combination of elements represent well-known,
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`routine, conventional activity only when the element(s) is widely prevalent or in common use in
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`the relevant industry. (MPEP § 2016.05(d).)
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`Thus, amended claims 1 and 7 and the claims dependent thereon are believed to recite
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`patent eligible subject matter in compliance with 35 U.S.C. §101.
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`New claims 13-17 are directed to a method of detecting the level of circulating glycodelin
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`in a mammal. Applicant respectfully submits that these claims recite patent eligible subject matter
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`in compliance with 35 U.S.C. §lOl.
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`Accordingly, reconsideration and withdrawal of the instant rejection is respectfully
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`requested.
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`Claim Rejection under 35 U.S.C. § 102
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`Claim 7 stands rejected under 35 U.S.C. § 102(a)(1) as allegedly lacking novelty in view
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`of Browne el a].
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`Without acquiescing to the rejection and in an effort to advance the examination of the
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`present application, Applicant has amended claim 7. Claim 7 has been amended to a method that
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`includes the step of determining the level of circulating glycodelin.
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`Browne el al. neither teaches nor suggests the use of glycodelin in a method to monitor
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`treatment of endometriosis in a mammal.
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`To anticipate a claim under 35 U. S.C. §102, a prior art reference must teach each and every
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`limitation of a claim. “A claim is anticipated only if each and every element as set forth in the
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`claim is found, either expressly or inherently described, in a single prior art reference.” Verdegaal
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`Bros. v. Union Oil Co. ofCalifornia, 814 F.2d 628, 631, 2 USPQ2d 1051, 1053 (Fed. Cir. 1987).
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`“The identical invention must be shown in as complete detail as is contained in the
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`claim.”
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`Richardson v. Suzuki Motor C0., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989).
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`Therefore, Applicant respectfully submits that claim 7 and all claims dependent thereon
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`are patentable over Browne el a]. under 35 U.S.C. §102.
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`Accordingly, reconsideration and withdrawal of the instant rejection is respectfully
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`requested.
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`Claim Rejection under 35 U.S.C. § 103
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`Claims 1-6 stand rejected under 35 U.S.C. § 103 as allegedly being obvious in view of
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`Browne el al., Ward el al. and Signorile el a].
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`As discussed above, Claim 1 as amended defines a method of diagnosing endometriosis in
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`a mammal comprising the steps of: determining the circulating levels of glycodelin in a plasma
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`sample from the mammal by contacting the sample with a glycodelin antibody raised in a host
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`animal, comparing the level of glycodelin to a pre-determined level associated with endometriosis,
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`and diagnosing the mammal with endometriosis when the levels of glycodelin is elevated to the
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`predetermined level associated with endometriosis.
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`None of the cited art teaches or suggests a method as claimed comprising detecting
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`circulating levels of glycodelin.
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`Ward el al., which was cited as relevant with respect to glycodelin (PAEP), teaches in
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`claim 43 (referred to by the Examiner) detecting the presence or absence of a gene associated
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`genetic marker correlated with endometriosis, wherein the gene “is selectedfrom any human gene
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`exceptfor a human gene of the following group ofhuman genes...” of which PAEP is one. Thus,
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`contrary to the Examiner’s assertion, Ward el al. does not teach or suggest screening of subjects
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`for endometriosis based on PAEP expression, but teaches excluding PAEP expression from
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`endometriosis determination.
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`Browne el al. and Signorile el al. are not relevant with respect to glycodelin. As set out by
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`the Examiner, Browne el al. relates to BDNF, and Signorile el al. is cited for teachings related to
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`ZAG.
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`Thus, claim 1 and the claims dependent thereon are believed to be both novel and inventive
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`in view of the cited references, and thus patentable over the prior art of record under 35 U.S.C. §
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`103.
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`Claims 8-10 and claims 11-12 stand rejected under 35 U.S.C. § 103 as allegedly being
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`obvious in view of the cited art. The Examiner alleges that in view of the art regarding biomarkers
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`(Browne el al., Ward el al. and Signorile el al.) and the Ahern el al., it would have been obvious
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`for one of ordinary skill in the art to compile the components of the claimed kit.
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`Applicant respectfully disagrees.
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`Claim 8 defines a kit comprising a glycodelin-specific reactant, a ZAG—speciflc reactant,
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`and optionally a BDNF- speciflc reactant for use in a method to diagnose endometriosis in a
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`mammal.
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`First of all, as set out above, Ward el 6!]. fails to teach the detection of circulating glycodelin
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`in a method of diagnosing endometriosis.
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`In addition, Browne el al.
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`teaches that neurotrophin 4 and 5, and BDNF were more
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`concentrated in biopsies from endometriosis patients than in controls. Browne el al. neither
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`teaches nor suggests that BDNF is a protein secreted by the endometrium and is silent with respect
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`to the determination of circulating BDNF levels, 1'.e. BDNF secreted into the circulating fluid. As
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`would be appreciated by one of ordinary skill in the art, tissue concentrations of proteins do not
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`necessarily correlate with circulating concentrations.
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`It was the inventors who have for the first time determined that BDNF is secreted into the
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`circulating fluid, and that circulating levels of BDNF correlate with endometriosis.
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`Signorile el al. teaches the use of circulating ZAG, serum albumin and complement C3
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`precursor as biomarkers for endometriosis.
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`Given the prior art of record, one of ordinary skill in the art would not have considered the
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`use of glycodelin and ZAG as biomarkers for the detection of endometriosis, much less preparing
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`a kit to determine these 2 biomarkers, and optionally BDNF.
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`In addition, Applicant wishes to point out that a simplistic combination of the cited art
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`references to arrive at the claimed invention would be contrary to established law. The mere fact
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`that references can be combined or modified does not render the resultant combination obvious
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`unless the results would have been predictable to one of ordinary skill in the art. KSR International
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`Co. v. Teleflex Inc., 82 USPQ2d 1385, 1396 (2007). Rejections on obviousness cannot be sustained
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`by mere conclusory statements; instead, there must be some articulated reasoning with some
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`rational underpinning to support the legal conclusion of obviousness. KSR, 550 US. at 418, 82
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`USPQ2d at 1396 quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
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`Furthermore, a statement that modifications of the prior art to meet the claimed invention
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`is n_ot sufficient to establish a primafacie case of obviousness without some objective reason to
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`combine the teachings of the references. Ex parle Levengood, 28 USPQ2d 1300 (Ed. Pat. App. &
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`Inter. 1993). If proposed modifications would render the prior art invention being modified
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`unsatisfactory for its intended purpose, then there is no suggestion or motivation to make the
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`proposed modification. In re Gordon, 733 F.2d 900, 221 USPQ 1125 (Fed. Cir. 1984). See also,
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`MPEP § 2143.01.
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`Thus, claim 8 and the claims dependent thereon are believed to be patentable over the cited
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`prior art under 35 U.S.C. § 103.
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`Accordingly, reconsideration and withdrawal of all rejections is respectfully requested.
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`U.S. Serial No.: 15/632,497
`Atty. Docket No.: GWLG-017US-CIP
`Response to Non-Final Office Action
`
`CONCLUSION
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`Applicant submits that all pending claims are in condition for allowance. It is believed that
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`all pending issues have been fully addressed. However, the absence of a reply to a specific
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`rejection, issue, or comment does not signify Applicant’s agreement. In addition, because the
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`arguments made above may not be exhaustive, there may be additional reasons for patentability of
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`any or all pending claims (or other claims) that have not been expressed. Further, the amendment
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`of any claim does not necessarily signify concession of unpatentability of the claim prior to its
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`amendment.
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`The Examiner is encouraged to contact the undersigned at the telephone number listed
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`below to discuss any issue believed to be relevant to this matter.
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`Respectfully submitted,
`MILSTEIN ZHANG & WU LLC
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`By:
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`/Yin P. Zhang 44,372/
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`
`Yin Philip Zhang, Ph.D., Reg. No. 44,372
`Attorney for Applicants
`Tel: (617) 529-8369
`Email: philip.zhang@mzwiplaw.com
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`Date: June 6 2018
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`Customer Number: 88993
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`MILSTEIN ZHANG & WU LLC
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`2000 Commonwealth Ave, Suite 400
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`Newton, MA 02466
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