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 .
Priority
The instant application, filed 02/09/2022, is a national stage entry of PCT/GB2019/052356, filed 08/21/2019.
Preliminary Amendments and Claim Status
The preliminary amendment filed on 08/12/2025 is acknowledged and entered.
Claims 50, 51, and 53 are cancelled;
Claims 1-49, 52, and 54-61 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/13/2022, 07/27/2022, 09/02/2022, and 04/209/2025 are acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election with traverse of Group I (claims 1-49 and 61) drawn to compounds of formula (I) and the compound of Example 32.13 as a species of a compound of Formula (I) in the reply filed on 08/12/2025 is acknowledged. It is noted that Applicant also elects vascular hyperpermeability as a species of a specific disease or condition in with Factor XIIa activity is implicated. However, since Applicant did not elect group II (claims 52 and 54-61), a species of a specific disease or condition was not required.
Applicant’s arguments filed on 08/12/2025 are found not persuasive. Applicant argues that the instant claims possess unity of invention because they are drawn to compounds and methods for using those compounds, falling within the categories of invention listed in 37 C.F.R. § 1.475 (b). However, the determination of a lack of unity was based on the lack of a special technical feature within the claims. According to MPEP § 1893.03 (d),
A group of inventions is considered linked to form a single general inventive concept where there is a technical relationship among the inventions that involves at least one common or corresponding special technical feature. The expression special technical features is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art.
Furthermore, according to MPEP § 1850 II,
Whether or not any particular technical feature makes a "contribution" over the prior art, and therefore constitutes a "special technical feature," should be considered with respect to novelty and inventive step. For example, a document discovered in the international search shows that there is a presumption of lack of novelty or inventive step in a main claim, so that there may be no technical relationship left over the prior art among the claimed inventions involving one or more of the same or corresponding special technical features, leaving two or more dependent claims without a single general inventive concept. Lack of unity of invention may be directly evident "a priori," i.e., before considering the claims in relation to any prior art, or may only become apparent "a posteriori," i.e., after taking the prior art into consideration.
According to the Restriction/Election requirement dated 02/13/2025, the shared technical feature of the instant claims does not rise to the level of a special technical feature, as it does not make a contribution over the prior art of record. The common technical feature of the instant claims is a compound of Formula (I), which does not make a contribution over the prior art of record according to the teachings of Evans et al. (WO 20110510672 A1, published May 5, 2011). Stated otherwise, the shared technical feature of the instant claims is known within the art. Therefore, the instant claims do not relate to a single general inventive concept under PCT rule 13.1, and lack a special technical feature. As such, the claims lack unity of invention a posteriori, i.e. in view of the prior art of record. Thus, the restriction requirement is still deemed proper, and is therefore made FINAL.
Claims 1-49, 52, and 54-61 are pending. Pursuant to 37 CFR § 1.142(b), claims 4-20, 23-30, 32, 34, 37, 38, 40-43, 47, 52 and 54-61 are withdrawn from consideration as being drawn to a nonelected species and non-elected invention. As such, claims 1-3, 21, 22, 31, 33, 35, 36, 39, 44-46, 48, 49, and 62 read on the elected species and are therefore under consideration.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Figure 1. Elected Species
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Figure 1. Applicant’s elected species, Compound 32.13, CAS Registry Number: RN 2614333-68-3
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicant’s elected species, Compound 32.13, also known as CAS Registry Number: RN CAS Registry Number: 2614333-68-3 REGISTRY Entered STN: 19 Mar 2021. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN CAS Registry Number: 2614333-68-3 REGISTRY, Entered STN: 19 Mar 2021 Entered STN: 19 Mar 2021] (Figure 1) makes a contribution over the prior art of record. Therefore, according to MPEP § 803.02: should the elected species appear allowable, the search of the Markush-type claim will be extended. The Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration. It has been determined that the entire scope claimed is not patentable.
Status of Claims
Upon examination, the elected species is found allowable based on the present record. In view of the allowability of the elected species, and in accordance with MPEP § 803.02, the search of the Markush-type claim has been extended to include a single nonelected species, identified as Example No. 17.02 of the instant specification (page 97). In view of the non-elected species, claims 4-8, 12, 13, 15, and 16 are rejoined as they read on Example No. 17.02. All claims drawn
to nonelected species remain withdrawn from consideration. Pursuant to 37 CFR § 1.142(b), claims 9-11, 14, 17-20, 23-30, 32, 34, 37, 38, 40-43, 47, 52 and 54-61 remain withdrawn from further consideration, as being drawn to a non-elected invention and species. As such, claims 1-8, 12, 13, 15, 16, 21, 22, 31, 33, 35, 36, 39, 44-46, 48, 49, and 62 read on the single nonelected species, to which the Markush-type claim has been extended, Example No. 17.02, and are therefore under consideration in the instant application, and being examined on the merits as such.
Claim Objections
Claims 21 and 22 are objected to for depending on a rejected claim (claim 1).
Claim Rejections - 35 U.S.C. § 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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8, 12, 13, 15, 16, 31, 33, 35, 36, 39, 44-46, 48, 49, and 62 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by Philippou et al. (WO 2019186164 A1, published October 3, 2019, cited on applicant IDS dated 05/13/2022), hereinafter Philippou.
The instant claims are drawn to a compound of Formula (I) and a pharmaceutical composition thereof.
Philippou teaches compounds which are modulators of Factor XIIa useful as anticoagulants. The teachings of Philippou directly anticipate the instant claims. In the extension of the search to a nonelected species, Philippou teaches Compound M05237 (page 189), also known as CAS Registry Number: RN 215452-95-2. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 215452-95-2. Entered STN: 10 Dec 1998], which corresponds to compound Example No. 17.02 of the instant specification (page 97). This nonelected species is also found in claim 48, as the last compound on page 65 of the amended claims, filed on 08/12/2025. Finally, Philippou teaches a pharmaceutical formulation comprising the compound and a pharmaceutically acceptable excipient (claim 30).
Regarding claim 1, Philippou anticipates a compound of formula (I) as claimed wherein,
Figure 2. Comparison of prior art compound and instantly claimed Formula (I)
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Fig 2. a) Philippou CAS Registry Number: RN 215452-95-2; b) instantly claimed Formula (I)
n is 1
Y is a bond
R1 and R2A together with the nitrogen atom to which R1 is attached, and the carbon atom to which R2A is attached form a five-membered saturated heterocycle
R2B is H
R3 is isoquinolinyl substituted with NH2, i.e., a fused 6,6-bicyclic ring containing one N and is substituted with one substituent that is NH2
A is –(C=O)R4
R4 is Formula (II)
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, wherein L is (CH2)2, P is NR11R12 wherein R11 and R12 are both H, and B is phenyl
Regarding claim 2, n is 1.
Regarding claim 3, A is –(C=O)R4.
Regarding claim 4, R4 is Formula (II)
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, wherein L is (CH2)2, P is NR11R12 wherein R11 and R12 are both H, and B is phenyl.
Regarding claim 5, P is NR11R12 wherein R11 and R12 are both H
Regarding claim 6, P is NRHR12
Regarding claims 7 and 8, P is NH2
Regarding claims 12 and 13, L is –(CH2)2—
Regarding claims 15 and 16, B is phenyl (i.e. aryl)
Regarding claim 31, R1 and R2A together with the nitrogen atom to which R1 is attached, and the carbon atom to which R2A is attached form a 5-membered saturated heterocycle
Regarding claim 33, Y is a bond
Regarding claim 35, 36, and 39, R3 is isoquinolinyl substituted with NH2, i.e., a fused 6,6-bicyclic ring containing one N and is substituted with one substituent that is NH2.
Regarding claims 44 and 45, R3 is
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Regarding claims 46 and 62, the chiral center *1 is in the (S) configuration enantiomer
Regarding claim 48, RN 215452-95-2 is the last compound on page 65 of the amended claims
Regarding claim 49, Philippou teaches a pharmaceutical formulation comprising the compound and a pharmaceutically acceptable excipient (claim 30).
A courtesy note to Applicant in the interest of compact prosecution: a number of withdrawn claims may also be rejected in view of the teachings of Philippou. Only the claims which read on the single nonelected species to which the Markush-type claim has been extended have been rejected in the instant office action. As such, amendments to claims beyond those rejected herein will be necessary to overcome the teachings of the prior art of record.
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623