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. Current Status of 18 / 550332 Claims 1-14, 17, and 18 are examined on the merits. Information Disclosure Statement The information disclosure statement (IDS) submitted on 2023 November 2 was submi tted in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner. 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. Claim s 11-14 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification is enabling for the treatment of diabetic retinopathy or hereditary angioedema with a compound of formula I and non-enabling for the treatment of the scope of diseases recited in claims 11-14 with a compound of formula I . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands , 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” ( Wands , 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” ( Wands , 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth herein below: The nature of the invention and (2) the breadth of the claims: The claims are drawn to treatment of a disease or disorder with a compound of formula I . Thus, the claims taken together with the specification imply that a compound of formula I can treat a disease recited in claims 11-14 . The state of the prior art and (4) the predictability or unpredictability of the art: SCHNEIDER ( Journal of Allergy and Clinical Immunology , 2007 , 120(2) , 416-422, cited in IDS) describes that ecallantide, a kallikrein inhibitor, can treat hereditary angioedema (abstract; page 420 , column 2, paragraph 2 to page 421, column 2, paragraph 3). CLERMONT ( Diabetes , 2011 , 60 , 1590-1598 , cited in IDS ) describes that plasma kallikrein contributes to retinal vascular dysfunction in diabetic rats (abstract). YOUSEF ( Endocrine Reviews , 2001 , 22(2) , 184-204) describes that more research is needed to understand the therapeutic benefit targeting plasma kallikrein (page 197, table 9 and section XI. Future Directions). The relative skill of those in the art: Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in treatment of the scope of diseases recited in claims 11-14 with a compound of formula I ). The amount of direction or guidance presented and the presence or absence of working examples: The specification has provided guidance for the treatment of diabetic retinopathy or hereditary angioedema with a compound of formula . The specification does not provide guidance for the treatment of the scope of diseases recited in claims 11-14 with a compound of formula I . The quantity of experimentation necessary : Considering the state of the art as discussed by the references above, particularly with regards to the treatment of the scope of diseases recited in claims 11-14 with a compound of formula and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims. 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 9 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. Compounds 1-52 should be directly recited within claim 9 because they are only present in the specification. Although the specification can be used to define how a term is defined in a claim, the specification can be amended and consequently the metes and bounds of compounds 1-52 can be changed as well. MPEP 2173.05(s) teaches the following: Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). When the MPEP teaching applied to claim 9, compounds 1-52 should be directly in claim 9, not only recites in the specification. Allowable Subject Matter Claim s 9 , 11-14 , and 18 are not allowed. Claims 1-8, 10, and 17 are free of the prior art of record. The following is a statement of reasons for the indication of allowable subject matter: LIM (WO 2015 /164038, published 2015 October 29 , cited in IDS ) describes example 1 (page 30, line 3 to page 32, line 18) . This compound does not anticipate or render obvious a compound of examined formula I because a heteroaryl group is not directly attached to a 1 H ‐ spiro[3,1 ‐ benzoxazine ‐ 4,3' ‐ pyrrolidin] ‐ 2 ‐ one ring system. ABDEL-MAGID ( ACS Medicinal Chemistry Letters , 2023 , 14 , 129-130) describes compound 10 (page 130). Although this compound meets the metes and bounds of examined formula I, it is not prior art because the reference was published 2023 January 17, which postdates the effective filing date of 2021 March 18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT NOBLE E JARRELL whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9077 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 9:00 AM to 5:00 PM . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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