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
Instant application 17/630,203 filed on 07/29/2022 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-37 are pending.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 09/12/2025 is acknowledged.
The traversal is on the ground(s) that there would not be . These arguments have been considered but are not found persuasive as such arguments do not apply when restriction is required under 35 USC 121 and 372, as in the instantly filed application. Thus, when the Office considers international applications as an International Searching Authority, as an International Preliminary Examining Authority, and during the national stage as a Designated or Elected Office under 35 U.S.C. 371, only PCT Rule 13.1 and 13.2 will be followed when considering unity of invention of claims of different categories without regard to the practice in national applications filed under 35 U.S.C. 111.
Further, Applicant submitted:
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As pointed by examiner in the restriction mailed on 07/16/2025, compounds of Formula (I) are common between Group I, Group II, Group III and Group IV.
The compounds of Formula (I) are not a special technical feature because compounds of Formula (I) have been disclosed in prior art.
As cited in the restriction mailed on 07/16/2025:
Harling (US-20190152946-A1, also published as WO-2017211924-A1) teaches degrading target proteins and the treatment of disorders mediated by the target proteins:
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Harling teaches and claims compounds of formula I comprising inhibitors targeting E3 ligase binder, linker and IRAK3 (also known as IRAK-M) binder (see claim 1):
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Thus, it is maintained that the technical feature linking the inventions of Groups I-IV does not constitute a special technical feature as defined by PCT Rule 13.2 and does not define a contribution over the prior art for the reasons of record.
Therefore, the instant claims are not so linked as to form a single general inventive concept and accordingly, the claims lack unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 32-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/12/2025.
However, Examiner will consider rejoinder after allowable matter is identified.
Applicant's election with traverse of compound 38 in the reply filed on 09/12/2025 is acknowledged
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In the office action mailed on 07/16/2025, examiner requested identification of claims readable on the elected species: “The reply must also identify the claims readable on the elected species, including any claims subsequently added.”
Since Applicant has not identified claims readable on the elected species, the examiner determined that the claims 23-31 does not read on the elected species. E3 ligase binder (E) moiety present in the elected species is defined in instant claim 15 and falls under formula (IV) (does not fall under formulas S1, I-1 and I-2, I-3, I-4, I-5, I-6, I-7 or I-9).
It should be noted that the elected species (compound 38) is not recited in instant claim 22.
Claims 22-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/12/2025
The species election is mainly for search purposes.
Examination will begin with the elected species. 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. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. 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. Id.
As per MPEP 803.02, the Examiner will attempt to determine whether the entire scope of the claims is patentable. Applicants' elected species, as shown above, does make a contribution over the prior art. Therefore, according to MPEP 803.02: should the elected species appear allowable; the search of the Markush-type claim will be extended. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The Examiner need not extend the search beyond a proper Markush grouping.
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.
Written Description
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, claims are drawn to a compound represented by formula (I) wherein the moieties have been only defined using functional language to describe the claimed chemical IRAK-M binder, linker and R3 ligase binder without adequate structure-function support.
The instant specification and instant claims do not provide sufficient description such that one could anticipate what structure falls under the recited formula (I).
Instant specification provides support for IRAK-M binders ((see examples 1-70, Table 2-1, page 189). However, for all the tested examples falls under instant formula (II) wherein X is S, Z is O and R03 is piperidine and R4 always comprise isoxazole moiety.
Applicant did not test a representative number of examples within all the structural moieties claimed. Therefore, the examples provided in the specification are not a representative number of the claimed genus.
Hubbard (Leah L.N. Hubbard, Bethany B. Moore, Infectious Disease Reports 2010; volume 2:e9) teaches that expression of IRAK-M can be altered in response to a number of molecules:
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However, IRAK-M binder is not a recognized class of compounds, and the instant specification do not provide sufficient description such that one could anticipate what structures fall under the IRAK-M binder moiety in instant formula (I).
Further, one of ordinary skill in the art would expect that selections of specific IRAK-M binder, specific linker and specific E3 ligase binder may lead to significant difference in functional activity of the constructed bifunctional compound.
Furthermore, regarding linkers, the instant specification provides examples of linkers (see examples 1-70, Table 2-1, page 189). However, the instant specification does not provide support for all possible linkers recited in instant claim 1.
One of ordinary skill would expect that structural changes in linkers can lead to a significant difference in functional activity.
For example, Troup (Troup et al., Explor Target Antitumor Ther. 2020;1:273-312) teaches that empirical trial and error is often required to design a linker for a specific pair of compounds (page 279):
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The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims do not resolve these issues, since these claims do not further limit or provide further structure of all moieties present in instant formula (I). For example, claim 7 limits IRAK-M binders to compounds of formula (III) and claim 15 limits E3 ligase binder to compounds of formula (IV), but no claim limits all moieties of instant formula (I). Accordingly, these claims are also rejected.
The rejection would be overcome by amending the claims to add specific structures of IRAK-M binders, specific linkers and specific structures of E3 ligase binders.
Improper Markush Grouping Rejection
Claims 1-21 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use.
A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of IRAK-M binder (M)r, Linker (L) and E3 ligase binder (E) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
In the present case, at least (1) applies. It cannot be said that all members of the Markush group have a single structural similarity. Specifically, the species of the Markush group do not share a “single structural similarity” because there are no required structural features within each compound of formula I which would have at least one structural feature, which feature is essential to the activity/function of the claimed compounds, in common.
In addition, at least (2) applies since each alternatively usable member of the Markush group does not share a common use. Rather, the specification discloses that the compounds are useful as E3 ligase binder, linker and IRAK-M binder; however, there is no common core in the compounds of formula (I) that are known as IRAK-M binder or E3 ligase binder. It is suggested that applicant amend the claims to contain only proper Markush groupings to compounds sharing a single structural similarity and a common use, wherein the common use shared by the compounds is a result of the structural similarity essential to the function of the compounds. For example, examiner suggest limiting E3 ligase binder to binders of formula (IV) and limiting IRAK-M binders to IRAK-M binders present in examples 1-70.
Further, regarding instant formula (II) recited in claim 3, the Markush grouping of R01, X, Y, Z, R03, A, R04 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity, as there is no common core, and a common use, as the specification fails to use a representative number of combinations of these variables for the use as IRAK-M binders.
The instant specification provides examples of IRAK-M binders. However, for all the tested examples (see examples 1-70, Table 2-1, page 189) X is S, Z is O and R03 is piperidine and R4 always comprise isoxazole moiety. Therefore, the examples provided in the specification are not a representative number of the claimed genus.
Dependent claims do not resolve these issues; therefore, those claims are also rejected. For example, claims 7, limit IRAK-M binder to compounds of formula (III) but does not provide any structural limitation to E3 ligase binders. Examiner suggest limiting E3 ligase binder to binders of formula (IV).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
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.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harling (WO-2017211924-A1).
Harling teaches and claims compounds of formula I comprising inhibitors targeting E3 ligase binder, linker and IRAK3 (also known as IRAK-M) binder (see claim 1):
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Harling teaches Protac compounds comprising IRAK3, E3 ligase binder and a linker (see claim 20).
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Further, Harling teaches E3 ligase IAP (Inhibitors of Apoptosis):
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Since the teachings of Harling meet all limitations of instant claims, those claims are anticipated.
Art Made of Record - Not Applied
Claims of US 11,639,354 B2 (also published as US 2021/0179614 A1, Jun. 17. 2021) recite IAPs (Inhibitors of Apoptosis Proteins) binders.
It should be noted that IAP (Inhibitor of Apoptosis Protein) binders are a specific class of E3 ligase binders.
Claims of US 11,639,354 B2 recite:
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Further, claims of US-12202829-B2 (also published as US 2023/0242529 A1, Aug. 3, 2023) recite IAPs (Inhibitors of Apoptosis Proteins) binders of formula (I):
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Conclusion
No claim allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/I.S./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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