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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/06/2025 has been entered.
Priority
This application claims priority to the U.S. National Stage (371) application of PCT/EP2019/086791 filed on 12/20/2019 which claims foreign priority to Foreign Application No. EP19194769.6 filed on 08/30/2019 and Foreign Application No. EP18215656.2 filed on 12/21/2018.
Claim Status
Claims 1-60, 68 and 70-75 are cancelled at the Applicant’s request. Claims 61 is currently amended, and the Applicant notes that no new matter is added. Claims 62-67, 69, 82, 84-92, 94-96, 98-107, 109-111, 113-117 are previously presented. Claims 76-81, 83, 93, 97, 108, 112 are withdrawn at the Applicant’s request. Claims 118-123 are new and the Applicant notes that no new matter is added.
Thus, claims 61-67, 69, 82, 84-92, 94-96, 98-107, 109-111 and 113-123 are pending and are under examination.
Withdrawn Rejections
The previous rejection of claims 61-67, 69 and 86-88 under 35 U.S.C. 103 as being unpatentable over Bergmann et al. (WO 2017 /182561 A1) in view of Rodgers et al. (WO 2014/021942 A1) and Widmann et al. (The Lancet Neurology, Volume 13, Issue 6, June 2014, Pages 630-636) is withdrawn in response to Applicant’s Amendments of claims and arguments.
The previous rejection of claims 82 and 84-85 under 35 U.S.C. 103 as being unpatentable over Bergmann et al. (WO 2017 /182561 A1), Rodgers et al. (WO 2014/021942 A1) and Widmann et al. (The Lancet Neurology, Volume 13, Issue 6, June 2014, Pages 630-636) as applied to claims 61 above, and further in view of “Rodgers 2” et al. (US 2002/0049162 A1) is withdrawn in response to Applicant’s amendments of claims and arguments.
The previous rejection of claims 89-92, 94-96, 98-107, 109-111 and 113-117 under 35 U.S.C. 103 as being unpatentable over Bergmann et al. (WO 2017 /182561 A1), Rodgers et al. (WO 2014/021942 A1) and Widmann et al. (The Lancet Neurology, Volume 13, Issue 6, June 2014, Pages 630-636) as applied to claims 61 above, and further in view of “Bergmann 2” et al. (WO 2019/081595 A2) is withdrawn in response to Applicant amendments of claims and arguments.
Claim Objections
Applicant is advised that should claim 109 be found allowable, claim 110 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 61-67, 69, 82, 84-92, 94-96, 98-107, 109-111 and 113-123 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting the amount or activity of DPP3 protein and treating a patient with hypotension for distributive shock using Angiotensin II, it does not reasonably provide enablement for treating a patient with hypotension for distributive shock using any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case where there is a relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. In the instant case, the use of different Angiotensin II analogues or variants to treat patients with hypotension for distributive shock is not well understood and is not documented in the prior art.
The current disclosure does not satisfy the enablement requirement for treating a patient with hypotension for distributive shock with any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II that are not commonly used for treating patients with hypotension for distributive shock and whether any necessary experimentation is "undue as discussed In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The breadth of the claims:
Claim 61 recites “A method for the treatment of distributive shock, comprising
administering to a subject experiencing hypotension an effective amount of an agonist that is an angiotensin-receptor agonist and/or a precursor thereof, wherein said subject has an amount of DPP3 protein and/or DPP3 activity in a sample of bodily fluid that is above a predetermined threshold, wherein said agonist is Angiotensin II, or an analogue thereof, or a hexapeptide or nonapeptide of Angiotensin II”.
Claim 61 is drawn to an angiotensin-receptor agonist without specifying what type of agonist to use. Claim 61 only lists the agonist as Angiotensin II, any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II. Claim 61 does not specify what sequence to use and the origin of each sequence if provided and thus the claim is recited at a high level of generality.
The nature of the invention:
The invention teaches detecting the amount of DPP3 protein or activity in a sample and treating a patient with hypotension for distributive shock using an agonist of angiotensin II receptor such as Angiotensin II, any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II. Distributive shock is commonly treated with vasopressors such as with epinephrine as noted in Cleveland Clinic (Cleveland Clinic, Distributive Shock, 04/16/2022, Retrieved on 20th of August of 2025: https://my.clevelandclinic.org/health/diseases/22762-distributive-shock). The chemical mechanism for treating a patient with hypotension for distributive shock using epinephrine is far different from the angiotensin II agonist pathway.
Even the prior art has shown that the agonist system is complex even at the level of one agonist of Angiotensin II and raises many questions as noted by Kimmoun et al. (Angiotensin II: a new approach for refractory shock management?, Critical Care 2014, 18:694, Page 1, Abstract; page 1, right column, “This first clinical trial on the use of angiotensin II in distributive shock raises many questions.”). Kimmoun does not teach using any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II to treat a patient with hypotension for distributive shock.
Thus, the nature of agonists of angiotensin II receptor is quite complex in regards to distributive shock and not much is known.
The state of the prior art:
The prior art is exploring the use of Angiotensin II to treat patients with distributive shock as noted by Kimmoun et al. (Abstract). Kimmoun teaches how Angiotensin II is used in a first clinical trial to treat a patient for distributive shock without affecting the cardiac output (Page 1, right column, second and third paragraphs). Although Kimmoun teaches that there might be a potential therapeutic use of angiotensin II to patients with hypotension for distributive shock, it falls short of using angiotensin II variants or analogues to treat a patient with hypotension for distributive shock. Kimmoun does not teach using any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II to treat a patient with hypotension for distributive shock
Thus, the prior art does not teach treating a patient with hypotension for distributive shock using angiotensin II analogues or variants.
The level of one of ordinary skill:
The prior art teaches using Angiotensin II to treat a patient with hypotension for distributive shock as noted by Kimmoun et al. (Abstract). Kimmoun teaches that only Angiotensin II is used in a first clinical trial to treat a patient with hypotension for distributive shock (Page 1, right column, second paragraph). Kimmoun does not teach using any Angiotensin II analogue or variant to treat a patient with hypotension for distributive shock.
Because the prior art does not teach using any of angiotensin II analogues or variants to treat a patient with hypotension for distributive shock, a skilled artisan would not have known how to use one of the Angiotensin II analogues or variants to treat a patient with hypotension for distributive shock nor what dose and treatment regimen to use for any Angiotensin II analogue or variant.
The level of predictability in the art:
As noted above, prior art does not teach a person of ordinary skill in the art on how to treat a patient with hypotension for distributive shock with any Angiotensin II analogue or variant. Kimmoun teaches treating a patient with hypotension for distributive shock only using Angiotensin II and notes that it still needs to be evaluated for its impact (Abstract). Kimmoun does not teach treating a patient with hypotension for distributive shock with any Angiotensin II analogue, any hexapeptide of Angiotensin II or any nonapeptide of Angiotensin II.
Furthermore, it is not known yet how will Angiotensin II analogue or variants affect the treatment response in patients with hypotension suffering from distributive shock.
There have not been any pharmacokinetic studies to indicate how will the patient response be with such agonists.
An analogue of a compound entitles a broad range of possibilities and structures that are not covered by the specification of the instant application. Similarly, a hexapeptide or a nanopeptide of a compound entitles a broad range of possibilities and structures. In the instant case, the claims read on any analogue of Angiotensin II, any hexapeptide of Angiotensin II or any nanopeptide of Angiotensin II.
Thus, there is a high level of unpredictability in the art because treating a patient with hypotension for distributive shock using Angiotensin II analogues or variants has not been documented as a common practice in prior art.
The amount of direction provided by the inventor:
The inventor provided directions on how to detect the amount of DPP3 protein or activity in a sample (Page 85-86, Examples 1 and 2). The inventor further provided directions on how to raise antibodies to epitopes on DPP3 and their effects on subjects with sepsis (Page 94, Example 5). The inventor did not provide any examples on how to combine the detection of DPP3 protein or activity in a patient with hypotension suffering from distributive shock with treatment using any Angiotensin II analogue or variant. Furthermore, the inventor did not provide directions for treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant.
The method of treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant is not specified i.e., route of administration of each type of angiotensin receptor agonists, dose of agonists and treatment regimen for each type of agonists. While angiotensin II has shown promise for treating patients with hypotension for distributive shock, the other types of angiotensin-receptor agonists have not been described.
Thus, the inventor provided no examples nor guidelines for an artisan on how to treat a patient with hypotension for distributive shock using any Angiotensin II analogue or variant.
The existence of working examples:
The working examples that the inventor has provided in the specification are for detecting the amount of DPP3 protein or activity in a sample, using DPP3 to prognose short-term mortality, purifying human native DPP3, raising antibodies to epitopes on DPP3 and their effects on subjects with sepsis (Specification, Examples 1-3, 5-7). The inventor did not provide examples for treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant.
Example 1 of the specification of the instant application teaches detecting the amount of DPP3 protein or activity in a sample (Pages 85-89, Example 1). Example 2 of the instant application teaches using DPP3 to prognose short-term mortality (Pages 90-91, Example 2). Example 3 of the instant application teaches purifying human native DPP3 (Pages 91-93, Example 3). Examples 5-7 of the instant application teach raising antibodies to epitopes on DPP3 and their effects on subjects with sepsis (Pages 94-101, Examples 5-7).
None of the listed examples that are cited above teach treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant. Furthermore, Examples 4-5 and 8-9 of the instant application do not teach treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant.
Thus, the inventor does not provide any working examples for treating a patient with hypotension for distributive shock using any Angiotensin II analogue or variant.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
As noted above, the inventor provided no examples or guidelines for an artisan on how to treat a patient with hypotension for distributive shock with any Angiotensin II analogue or variant. The inventor only provided examples for detecting the amount of DPP3 protein or activity in a sample, using DPP3 to prognose short-term mortality, purifying human native DPP3, raising antibodies to epitopes on DPP3 and their effects on subjects with sepsis (Specification, Examples 1-3 and 5-7).
Furthermore, all the Examples of the instant case do not teach how to treat a patient with hypotension for distributive shock with any Angiotensin II analogue or variant. Last, the prior art falls short of teaching how to use different Angiotensin II analogues or variants to treat a patient with hypotension for distributive shock.
Thus, there will be an undue amount of experimentation to be done by the skilled artisan based on the state of prior art and inventor’s guidelines of the instant case.
The specification fails to disclose at least one method for using the claimed invention that bears a reasonable correlation to the entire scope of the claim, and thus the enablement requirement of 35 U.S.C. 112 is not satisfied. In the instant case, the specification teaches detecting the amount of DPP3 protein or activity in a sample; however, it does not disclose any methods for treating patients with hypotension for distributive shock with any Angiotensin II analogue or variant.
Response to Arguments
Applicant’s arguments and amendments, see Remarks and Amendments of Applicant’s Response, filed 11/06/2025, with respect to claims 61-67, 69, 82, 84-92, 94-96, 98-107, 109-111 and 113-117 have been fully considered and are persuasive. The previous rejection of claims 61-67, 69, 82, 84-92, 94-96, 98-107, 109-111 and 113-117 under 35 U.S.C. 103, regarding obviousness, has been withdrawn.
However, Applicant's amendment necessitated a new ground of rejection presented in this Office action.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678