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 was received 03 May 2024; it is a national stage application of PCT/CN2022/129952, filed 04 November 2022, and claims foreign priority to CN202111306535.8, filed 05 November 2021. Acknowledgment is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
Restriction/Election
Requirement for Restriction/Election was mailed 02 June 2026.
Applicant’s Response to Requirement for Restriction/Election was received 03 August 2026. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Applicant’s election of Group I (Claims 1-11) and Compound No. 5-17, indicating claims 1-5 and 9-11 read on the elected species, in the Response filed 03 August 2026 is acknowledged. Compound 5-17 (Claim 10, p. 132) is shown below. Applicant’s request in the Response that the claims in Group II be considered for rejoinder should the claims in Group I be found allowable, and the non-elected species be reinstated, is acknowledged.
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The claims in Group II (Claims 12-13) are withdrawn.
The claims which do not read on the elected species, claims 6-8, are also withdrawn.
In accordance with 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.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable.
Status of the Claims
The listing of claims filed 03 May 2024 has been examined.
Claims 1-13 are pending.
Claims 6-8 and 12-13 are withdrawn.
Claims 1-5 and 9-11 are examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 03 May 2024 is acknowledged and has been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains a phrase which can be implied, specifically, “Disclosed in the present application…” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 4-5 and 10-11 are objected to because of the following informalities:
Claim 11 recites, “A pharmaceutical composition, wherein the composition contains an effective amount of the compound of claim 1, or its pharmaceutically acceptable salt, prodrugs, and a pharmaceutically acceptable carrier.” The word “or” appears to be missing. Examiner suggests amending to, “…or its pharmaceutically acceptable salt or prodrugs, and a pharmaceutically acceptable carrier.” [Emphasis added.] or similar.
Examiner interprets R21 in claims 4-5 and R5 in claim 1 as referring to the same variable group and, for clarity, Examiner requests all instances wherein the same variable group is recited use the same terminology. (See rejection under 112(d) below.) Accordingly, Examiner requests “R21” be amended to “R5”.
Regarding claim 10, some structural elements in Compound Nos. 6-01, 6-02, and 6-03 are blurry. Examiner requests clearer images be provided.
Appropriate correction is requested.
Claim Rejections - 35 USC § 112(a)
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 11 is 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 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.
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 of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, claim 11 recites, “A pharmaceutical composition, wherein the composition contains an effective amount of the compound of claim 1, or its pharmaceutically acceptable salts, prodrugs, and a pharmaceutically acceptable carrier.” [Emphasis added.] Particularly, the term “prodrug” invokes the 35 U.S.C. 112(a) rejection. Even a cursory calculation of the number of compounds embraced in the instant claims would result in thousands of compounds.
Level of Skill & Knowledge in the Art
The level of skill and knowledge in the art is high.
Partial Disclosure
Compounds of Formula I have been disclosed and example compound species that would be within the general formula have been disclosed. However, as to the claimed prodrugs, no specific examples are given that would demonstrate possession or put the public in possession of all the claimed prodrugs of Formula I. It is generally accepted that prodrugs may vary by chemical formulae and may also differ in properties and the arrangement of atoms in the molecule.
Physical and/or Chemical Properties/Functional Characteristics
The instantly claimed compounds of Formula I, and prodrugs thereof, are compounds which allegedly degrade GSPT1 (Specification, p. 1, Technical Field). Although the art recognizes generally accepted definitions, the term “prodrug” is not explicitly defined by the Specification in such a way as to demonstrate that the inventors had possession of the prodrug of Formula I.
A review of the prior art identifies Najjar (Anas Najjar & Rafik Karaman (2019) Successes, failures, and future prospects of prodrugs and their clinical impact, Expert Opinion on Drug Discovery, 14:3, 199-220), which discloses successes and failures of prodrugs of known pharmaceuticals (p. 212, 3. Previous failed prodrugs). Najjar teaches hetacillin, an ester prodrug of ampicillin, which was withdrawn since it did not have a superior advantage when compared to ampicillin. In light of Najjar, it is unknown which of the prodrugs of compounds of formula (I) claimed by Applicant will be active or inactive. Further, one of ordinary skill in the art would not be able to predict which compounds, of the vast number that are claimed, will be active or inactive absent evidence. There is no structure/function correlation in the Specification showing which prodrugs would or would not be active.
Since Applicant has not set forth compounds or substituents on Formula I in the Specification which Applicant considers to be prodrugs, it is not clear what compounds fall under Formula I. Applicant has not described which prodrugs have the ability to degrade GSPT1 and which prodrugs lack said ability. Stated differently, there is no structure/function correlation and no representative number of specific examples of prodrugs that demonstrate which compounds retain activity. Further, one of ordinary skill in the art would not be able to predict the biological activity of the claimed prodrugs of Formula I.
Predictability of the Art
Medicinal chemistry is an experimental science with a low predictability level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity. Regarding prodrugs, predicting if a certain claimed compound retains the activity and function of the original drug is filled with experimental uncertainty because prodrugs contain variation by chemical and physical properties of the molecules.
Method of Making the Claimed Invention
Although the Specification provides methods for making compounds of Formula I (p. 43, Example 1 (4-85); p. 46, Example 2 (4-127)), no method for making all of the compounds, including prodrugs, encompassed by the instant claims has been disclosed. Methods of synthesizing compounds are, in general, known to a person of ordinary skill; however, methods of making the myriad of compounds encompassed by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as prodrugs, are merely described partially.
As such, the instant Specification and instant claims do not provide sufficient description such that one could anticipate which additional elements may or may not be present in the prodrugs of Formula I because the examples illustrated in the experimental section are limited to only compounds of Formula I.
Written Description Conclusion
Substantial and undue experimentation would be needed to practice Applicant’s invention because the Specification lacks sufficient detail to show how to use the prodrugs of the instant invention. Further, there is no guarantee that all of the prodrugs embraced by the scope of the claims would degrade GSPT1.
Even with the undue burden of experimentation, there is no guarantee that one would obtain the product of a desired prodrug of an instant compound of Formula I. Although some functional characteristics are disclosed or would be known to one of ordinary skill in the art, in the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed prodrugs in the instant application.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. It is unquestionable that the claims are broad and generic with respect to all possible compounds encompassed by the claims. In other words, the possible structural variations are limitless to any prodrugs of the genus. In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. The Specification does not provide sufficient descriptive support for all the myriad of compounds embraced by the claims, such as prodrugs of Formula I.
The description requirement of the patent statute 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 inventors, at the time the application was filed, had possession of the entire scope of the claimed invention. This rejection would be overcome by amending the claims to remove the term, “prodrug”.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-5 and 9-10 are 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.
Claim 1 recites, “…or R3 and R4 is connected into a ring (Preferably, a 3- to 20- membered ring, either non-substituted or substituted by 1-3 substituents, which can be saturated, unsaturated carbon ring, or a heterocyclic ring) ;…” and, “…single or multi-halogenated C1-4 alkyl (like -CF3),…” [Emphasis added.] Regarding claim 1, the terms "preferably" and “like”, as well as the parentheses, render the claim indefinite because it is unclear whether the limitations following the “preferably” or “like” or the terms contained inside parentheses are part of the claimed invention. See MPEP § 2173.05(d). Examiner suggests deleting the parentheses and the terms “preferably” and “like”.
Claims 2-5 and 9-10 are included in this rejection for depending on a rejected base claim (i.e., Claim 1) without resolving the issue.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4-5 and 10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4, which depends upon claim 1, recites the general structure Formula I’’, shown below:
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In Formula I’’, R0 is NR1R2 wherein R2 is (CH2)nC(O)R5 and n is 0. Accordingly, the new variable “R21” introduced in Formula I’’ corresponds to R5.
Claim 1 recites, “…R5 is independently selected from: H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, 3- to 8-membered heterocyclic groups, aryl, heteroaryl, NR7R8;…” However, claim 4 states R21 (i.e., R5) can be “OR22”. Accordingly, claim 4 improperly broadens the scope of claim 1 by indicating R21/R5 can be OR22.
Similarly, claim 5, which also depends upon claim 1, recites “R21” may be OR22. Accordingly, claim 5 improperly broadens the scope of claim 1 by indicating R21/R5 can be OR22.
Claim 10, which depends upon claim 1, recites several structures which are not encompassed by claim 1. For example, Compound No. 4-117, shown below:
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Wherein both R3 and R4 are H. However, claim 1 recites, “…R3 is selected from: C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, 3- to 8-membered heterocyclic groups, aryl, heteroaryl, C(O)R9;… or R2 or R3 is connected into a ring;…” Thus, according to claim 1, R3 cannot be H. Consequently, claim 10 improperly broadens the scope of claim 1 by indicating R3 can be H.
Applicant may cancel the claims, amend the claims to place them in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 USC § 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)(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 1-3 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry Number: 2402712-98-3 (Entered STN: 08 Jan 2020).
Regarding claims 1-3 and 9, CAS Registry Number: 2402712-98-3 teaches the following compound:
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Wherein R0 is NR1R2, R1 is H, R2 is halogen- and methyl-substituted aryl, R3 is C1 alkyl, R4 is H, m1 is 0, m2 is 0, m3 is 0, and m4 is 1.
Claims 1-3 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Muller (CN 102264720 A; IDS dated 03 May 2024, Cite No. 1).
Regarding claims 1-3 and 9, Muller teaches the following compound (Original, p. 30, ¶ [0122]; Translation, p. 10, Col. 1, Row 2):
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Wherein R0 is NR1R2, R1 is H, R2 is H, R3 is Cl-substituted phenyl, R4 is H, m1 is 0, m2 is 0, m3 is 0, and m4 is 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Muller (CN 102264720 A; IDS dated 03 May 2024, Cite No. 1).
Regarding claims 1-3 and 9-10, Muller teaches all of the claimed elements as stated above. Furthermore, Muller discloses general Formula IV (Translation, p. 9), shown below:
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Wherein n is 0 or 1, R8 and R9 can be hydrogen (Translation, p. 9, Last Line – p. 10, Line 1). Additionally, Muller discloses several exemplary compound of Formula IV (p. 10, Top), shown below:
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Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Muller would have found it prima facie obvious to prepare an instantly claimed compound of Formula I recited by claim 10 because Muller discloses structurally similar compounds and indicates R8 and R9 can be hydrogen and n can be 0 or 1 in Formula IV. For example, instant claim 10 discloses Compound No. 5-15-2, shown below:
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A skilled artisan, guided by Muller’s exemplary compounds, would have been motivated to change the Cl in
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to H while searching for structurally similar compounds because Muller teaches the variable R8 in Formula IV can be halogen or hydrogen (Translation, p. 9, Last Line) and discloses compounds having general Formula IV are useful as cancer therapies.
Regarding claim 11, Muller teaches all of the claimed elements as stated above. Furthermore, Muller teaches isoindoline compounds, which are useful in the treatment of various diseases, as well as pharmaceutical compositions comprising said compounds (Translation, p. 1, FIELD OF THE ART.) The composition may further comprise one or more excipients (Translation, p. 24, Last Line), stating, “...the pharmaceutical compositions and dosage forms are prepared by thoroughly mixing the active ingredient with a liquid carrier, a fine solid carrier, or both…” (Translation, p. 26, ¶ 1).
Muller does not explicitly teach an exemplary composition comprising an instantly claimed compound of Formula I.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Muller would have found it prima facie obvious to prepare a pharmaceutical composition comprising an instantly claimed compound of Formula I because Muller discloses such a compound, as well as similar compounds, suggesting such compounds are useful as chemotherapies (Translation, p. 1-2), and suggests preparing a pharmaceutical composition comprising such compounds.
Conclusion
Claims 1-5 and 9-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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