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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a compound of Formula (I), and the compound, (R)-3-(4-((R)-3-(4-(1-(4-((5-bromo-4-((5-(dimethylphosphoryl)-2-ethylquinolin-6-yl)amino)pyrimidin-2-yl)amino)-2-ethyl-5-methoxyphenyl)piperidin-4-yl)piperazine-1-carbonyl)pyrrolidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione, having the formula:
PNG
media_image1.png
11
1
media_image1.png
Greyscale
in the reply filed on April 27, 2026 is acknowledged. The traversal is on the ground(s) that the search and examination of three groups do not present an undue burden to the Office, because the method claims ultimately depend from and include all of the limitations drawn to the claimed compounds. This is not found persuasive because Inventions I and II, Inventions I and III, Inventions II and III as set forth in the previous Office Action mailed on February 27, 2026 are independent or distinct. In summary, the product as claimed can be used in a materially different process, such as in vitro assays and shelf-life testing; and the inventions II and III are not capable of used together, because binding and altering the specificity of cereblon complex do not require the performance of treating a disease in a subject and does not require the active step of administering the compound of Formula (I) to a subject. As such, there would be an examination burden as these distinct inventions would require different filed of search (e.g., searching different classes/subclasses or electronic resources, or employing different search queries). There would also be an examination burden for the patently distinct species, because the species of compound of Formula (I) and the method species has distinct characteristics and/or structure that would require the use of different search queries; Additionally, the method species involves different patient population that would also require the use of different search queries. Given these reasons addressed above, the requirement is still deemed proper and is therefore made FINAL.
Claims 2, 16, 35, 44, 66 and 90-96 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on April 27, 2026.
Please note the claim does not recite the name and the structure of the elected species of compound of Formula (I); However, Applicant noted the elected compound species has the definition of the exact substitutions indicated on p.4 to p. 6 of the reply.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected compound species conducted by the Examiner discover a prior art (CAS Registry Number 1267777-90-1) that anticipates the claimed invention; and a prior art by Zhao et al. (WO 2021/036922 A1, cited in the IDS filed on December 30, 2024; WIPO counterpart to US 2022/0306659 A1, cited in PTO-892) that renders obvious the claimed invention. In light of this discovery, the search is expanded to the subject matter of the compound of formula (I) to include compound having the CAS Registry Number 1267777-90-1 and the subgenus of the elected compound species having the structure of:
PNG
media_image2.png
340
532
media_image2.png
Greyscale
in addition to the elected compound species, such that it does not encompass the full scope of the claim(s).
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on February 12, 2024, wherein
Claims 1-14, 16-20, 35, 44, 66, 88 and 90-96 are pending.
Claims 2, 16, 35, 44, 66 and 90-96 are withdrawn.
Claims 1, 3-14, 17-20, and 88 are under examination in accordance with the elected species along with the expanded compound species set forth in the Expansion of Election of Species Requirement section above.
Priority
The instant application 18/391,154 filed on December 20, 2023 is a continuation of 371 of PCT/CN2022/100017 filed on June 21, 2022, which claims priority to, and the benefits of Foreign Patent Application No. PCT/CN2021/101281 filed on June 21, 2021, and Foreign Patent Application No. PCT/CN2021/142802 filed on December 30, 2021.
Receipt is acknowledged of certified copy of the PCT/CN2021/101281 as required by 37 CFR 1.55.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on June 21, 2021. It is noted, however, that applicant has not filed a certified copy of the PCT/CN2021/142802 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/30/2024, 03/12/2025, 10/23/2025, 01/05/2026, and 04/26/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The spacing of the lines of the specification is such as to make reading difficult. New application papers with lines 1 1/2 or double spaced (see 37 CFR 1.52(b)(2)) on good quality paper are required.
Claim Objections
Claim 88 is objected to because of the following informalities:
Regarding claim 88, the recitation of “[a]pharmaceutical composition comprising a compound” is missing a comma between the term “composition” and “comprising”.
Appropriate correction is required.
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 1, 3-14, 17-20, and 88 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 specification does not disclose identifying structural features common to substantially all members of the claimed genus that would permit one of ordinary skill in the art to distinguish compounds expected to posses the claimed target-binding functionality from compounds outside the genus. The disclosure fails to establish a predictive relationship between the Warhead structure and the recited target-binding function across the full scope of the claimed genus.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
According to MPEP 2163 I, “[t]o satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116… An applicant shows that the inventor was in possession of the claimed invention 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 v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991)”.
Additionally, according to MPEP II-A-3-a-ii, “[t]he written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”; “[a] ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).”; and “’[a] patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
In the present case, instant claim 1 recites “[a] compound of Formula (I):
PNG
media_image3.png
117
525
media_image3.png
Greyscale
; or a pharmaceutically acceptable salt, deuterated analog, or prodrug thereof, warhead is a targeting moiety that binds to a target protein; wherein the target protein is a mediator of a disease in a subject; Linker is a divalent chemical group that connects the Warhead moiety and the
PNG
media_image4.png
91
131
media_image4.png
Greyscale
moiety…”. In addition, instant claim 18 recites the function of the Warhead shown below:
PNG
media_image5.png
444
722
media_image5.png
Greyscale
; and instant claim 19 also recites the function of Warhead shown below:
PNG
media_image6.png
360
722
media_image6.png
Greyscale
PNG
media_image7.png
472
728
media_image7.png
Greyscale
. The claim(s) promises a broad genus of compound of formula (I) and a broad genus of pharmaceutically acceptable salt and deuterated analog, and prodrug thereof. The claim(s) also promises a broad function genus for the Warhead moiety of formula (I), such that said Warhead moiety binds to a broad genus of target protein.
In contrast, the specification only exemplifies Compound 1-60, B34, B35, B37, B38, C41, and D42 (see e.g., p. 39-42). Please note Compound B33, B36, C39, C40 are not a claimed compound of Formula (I). It is noted that Compound 1-15 and 33-60 are compound having the structure of
PNG
media_image8.png
142
188
media_image8.png
Greyscale
, i.e., compound of formula (I) without a warhead and linker; and they all have the
PNG
media_image9.png
74
108
media_image9.png
Greyscale
moiety in common. Compound 16-29 all share the circled structure:
PNG
media_image10.png
189
350
media_image10.png
Greyscale
in common; Compound 31-32 all share the core structure of:
PNG
media_image11.png
146
181
media_image11.png
Greyscale
in common; Compound B33-B38 all share the circled structure:
PNG
media_image12.png
107
431
media_image12.png
Greyscale
in common; C41 has the structure of:
PNG
media_image13.png
172
336
media_image13.png
Greyscale
and D42 having the structure of:
PNG
media_image14.png
164
132
media_image14.png
Greyscale
. The specification only tested some of these compound species of Formula (I) for their EGFR and BTK degradation activity in HTRF assay (see e.g., Test Example 1). In other words, the specification only exemplified two species of
PNG
media_image8.png
142
188
media_image8.png
Greyscale
(i.e.,
PNG
media_image15.png
99
161
media_image15.png
Greyscale
and
PNG
media_image16.png
107
158
media_image16.png
Greyscale
) in combination with the following
PNG
media_image17.png
50
74
media_image17.png
Greyscale
species having the core structure of:
PNG
media_image18.png
178
121
media_image18.png
Greyscale
,
PNG
media_image11.png
146
181
media_image11.png
Greyscale
,
PNG
media_image19.png
106
237
media_image19.png
Greyscale
,
PNG
media_image14.png
164
132
media_image14.png
Greyscale
, or
PNG
media_image20.png
155
161
media_image20.png
Greyscale
.
While Applicant does not have to exemplify every possible compound species having the structure of:
PNG
media_image3.png
117
525
media_image3.png
Greyscale
to satisfy the written description requirement; However, applicant needs to provide enough representative species from different corners of the range (
PNG
media_image21.png
74
122
media_image21.png
Greyscale
,
PNG
media_image22.png
68
176
media_image22.png
Greyscale
, and
PNG
media_image8.png
142
188
media_image8.png
Greyscale
) to represent the claimed genus fairly. In other words, while applicant does not necessarily need to exemplify every single species of Formula (I), applicant should give concrete examples that reflect the diversity of what they are claiming. Since the claims recite a large set of possible Warhead, Linker, S1, S2, Z1, Z2, Z3, R1, and R2 along with a functional language for the Warhead (i.e., “Warhead is a targeting moiety that binds to a target protein; wherein the target protein is a mediator of a disease in a subject”), encompassing any targeting moiety capable of binding to any target protein that mediates any disease in any subject, Applicant must provide a reasonable sampling of them —a representative number of compound species—so that a relevant artisan can see applicant truly envisioned the whole range, i.e., the entire scope of Formula (I) having the structure of:
PNG
media_image3.png
117
525
media_image3.png
Greyscale
. Applicant also needs to provide a reasonable sampling of Warhead —a representative number of Warhead species— in Formula (I) and the function(s) of these Warhead species so that a relevant artisan can correlate the chemical structure of Warhead with the function characteristics, and envision that applicant is the possession of the entire scope of Warhead capable of binding to any target protein that mediates any disease in any subject.
In sum, the disclosed species are concentrated within a limited number of structural subclasses and do not adequately represent the breadth of variation encompassed the claimed Warhead, linker, target-binding functionalities.
With respect to “deuterated analog, or prodrug thereof” in the claim(s), the specification does not reasonably convey to one of ordinary skill in the art that Applicant was in possession of the full scope of the claimed “deuterated along, or prodrug thereof” at the time of filing because the disclosure fails to identify any particular deuterated along species, or prodrug species of compound of Formula (I), synthetic preparation, or representative examples thereof, aside from a broad recitation that any derivative of an active agent that requires a transformation within the body to release the active agent, and any compound of Formula (I) with deuterium substitution are contemplated for use in the invention. The mere boiler plate reference to “deuterated analog, prodrug thereof” does not provide adequate blaze marks to the vast genus encompassed by the claims.
In sum, no guidance identifying which positions may be substituted while retaining claimed activity, no representative deuterated species spanning across the claimed genus, no demonstrated possession of deuterated embodiments across varying Warhead-linker combinations.
The specification does not reasonably convey to one of ordinary skill in the art that Applicant was in possession of the full scope of the claimed “prodrug” at the time of filing because the disclosure fails to identify any particular deuterated species, positions of deuterium incorporation, degrees of deuteration, synthetic preparation, or representative examples thereof. The mere boilerplate reference to “deurated forms” does not provide adequate blaze marks to the vast genus encompassed by the claims.
Therefore, in view of the foregoing, applicant is not in the possession of the entire scope of
PNG
media_image3.png
117
525
media_image3.png
Greyscale
; or a pharmaceutically acceptable salt, deuterated analog, or prodrug thereof.
This is a written description rejection.
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, 3-14, 17-20, and 88 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.
Regarding claim 1,
the recitation of “
PNG
media_image23.png
139
697
media_image23.png
Greyscale
” renders the claim indefinite, because the claim appears to encompass chemically impossible or undefined structure in which the trivalent carbon (-C=) at Z1, Z2, or Z3 is bond to a hydrogen and to the
PNG
media_image24.png
54
248
media_image24.png
Greyscale
moiety. It is noted for that instance, the carbon atom in the aromatic ring is forming two additional covalent bonds, which exceeds basic bonding rule in chemistry. Therefore, one skilled in the art would not reasonably be apprised of the metes and bounds of the claimed compound. In order to advance prosecution, the Examiner is interpreting the claim in light of the elected compound species, such that
PNG
media_image25.png
63
59
media_image25.png
Greyscale
is
PNG
media_image1.png
11
1
media_image1.png
Greyscale
.
The recitation of “
PNG
media_image26.png
114
158
media_image26.png
Greyscale
…linker is a divalent chemical group that connects the Warhead moiety and the
PNG
media_image27.png
99
126
media_image27.png
Greyscale
moiety… s2 is 0 or 1” renders the scope of the claim unclear. The claim does not specify how a single compound of formula (I) is formed when there is no linker linking the Warhead moiety and the
PNG
media_image27.png
99
126
media_image27.png
Greyscale
moiety, and that can lead to various interpretations. For instance, the claimed compound can be interpreted such that (i) the compound is a mixture consisting a warhead compound and a compound having the structure of:
PNG
media_image27.png
99
126
media_image27.png
Greyscale
with no attachment; or (ii) a warhead compound is directly bond to
PNG
media_image26.png
114
158
media_image26.png
Greyscale
. The lack of clarity renders the claim indefinite, because one of ordinary skill in the art cannot reasonably determine the metes and bounds of the claimed compound.
Accordingly, claims 3-14, 17-20, and 88 are rejected based on their dependency on a rejected base claim.
Regarding claim 9,
the recitation of “
PNG
media_image28.png
79
271
media_image28.png
Greyscale
…R12 is independently hydrogen… n….are each independently …1, 2, or 3” renders the claim indefinite, because the structural formula does not clearly identify whether the position labeled R12 represents an open substitutable valence or a carbon atom already saturated by an implicit hydrogen under conventional chemical drawing conventions. Thus, the claim can be interpreted either as (i) R12 replacing an implicit hydrogen atom at the ring position, or (ii) R12 being added in addition to the already implied valence state of the ring carbon. Accordingly, one of ordinary skill in the art would not reasonably be apprised of the metes and bounds of the claimed structure with reasonable uncertainty.
Regarding claim 18,
the limitation(s) in the parenthesis shown below (see shaded):
PNG
media_image29.png
450
734
media_image29.png
Greyscale
renders the claim indefinite, because it is unclear whether the limitation(s) recites in the parenthesis is merely exemplary, or a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites
the broad recitation “proteins pertinent to the integrated function of a cell”, and the claim also recites “proteins involved in catalytic activity, aromatase activity, motor activity, helicase activity, metabolic processes…. and proteins involved in transport”, which is the narrower statement of the range/limitation; and
the broad recitation “protease”, and the claim also recites “HIV 1 protease… NS3 protease… rhinovirus 3C protease… cytomegalovirus (CMV) protease” which is the narrower statement of the range/limitation
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Same logic applies to the phrase of “protein transporter activity, nuclear transport, ion transporter activity, channel transporter activity, carrier activity, permease activity, secretion activity, electron transporter activity, pathogenesis, chaperone regulator activity, nucleic acid binding activity, transcription regulator activity, extracellular organization and biogenesis activity and translation regulator activity” recites in the parenthesis. If the parenthesis is deleted, the phrase recites therein is also a narrow statement of the range/limitation; and the claim is also considered indefinite for the same reason.
Regarding claim 19,
the limitation(s) in the parenthesis shown below (see shaded):
PNG
media_image30.png
366
726
media_image30.png
Greyscale
PNG
media_image31.png
476
724
media_image31.png
Greyscale
renders the claim indefinite, because it is unclear whether the limitation(s) recites in the parenthesis is merely exemplary, or a required feature of the claims. If parenthesis is removed, the claim is also considered indefinite, because the limitation recites in the parenthesis is a narrower statement of the range/limitation recited beforehand; and it is not clear if the narrower language is merely exemplary, or a required feature of the claims. Please note description of examples or preference is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of the claim.
The recitation of “the” apoptosis pathway shown below:
PNG
media_image32.png
54
700
media_image32.png
Greyscale
renders the claim indefinite, because there is insufficient antecedent basis for this limitation in the claim. It is not clear is what “apoptosis pathway” is being referred to therein. Additionally, “other” partners appears to be a relative term, the term “other” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree. One of ordinary skill in the art would not reasonably apprised of the scope of “other partners in the apoptosis pathway”.
where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “influenza” is used by the claim to mean “a target protein,” while the accepted meaning is “a viral infection”. In other words, the term “influenza” is not used in the art to refer to a protein. Thus, the term is indefinite because the specification does not clearly redefine the term.
a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “tyrosine kinases”, and the claim also recites “tyrosine kinase p561ck”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 1, 3-14, 17-20, and 88 are rejected on the judicially-created 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). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The Markush grouping of the compound of Formula (I) is improper, because the alternatives defined by the Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
Instant claim 1 recites “[a] compound of Formula (I):
PNG
media_image3.png
117
525
media_image3.png
Greyscale
; or a pharmaceutically acceptable salt, deuterated analog, or prodrug thereof, warhead is a targeting moiety that binds to a target protein; wherein the target protein is a mediator of a disease in a subject; Linker is a divalent chemical group that connects the Warhead moiety and the
PNG
media_image4.png
91
131
media_image4.png
Greyscale
moiety…”. The Markush grouping of compound of Formula (I) includes vast variety of alternated compound species that do not share a substantial structural feature in common, they also do not share a common use that flows from the substantial structural feature. In the present case, the structure circled as follows:
PNG
media_image33.png
114
148
media_image33.png
Greyscale
is the only structure feature that shared among the Markush grouping of compound of Formula (I), and that does not constitute a substantial portion of the compound as a whole. According to Fujie et al. (US 6303264), glutarimide is an acid imide compound derived from an aliphatic dibasic acid that can be employed to form a resist composition used for production of semiconductor devices (see e.g., claims 1, 4, and 11-13; abstract). In other words, glutarimide (
PNG
media_image34.png
200
400
media_image34.png
Greyscale
) is taught to have a different use and is not taught to have engagement with any E3 ubiquitin ligase, bind to any protein of interest, and degrade any protein. Therefore, it is not apparent that this common structure feature alone, i.e., glutarimide, shared among all the compound species of Formula (I) contributes to the substantial feature essential for the compound to have the desired property of engaging with any E3 ubiquitin ligase, binding to any protein of interest, and degrading any protein.
Instant claim 8 further recites “wherein the compound is of Formula (II)
PNG
media_image35.png
111
489
media_image35.png
Greyscale
” encompassing a vast variety of Linker and Warhead alternatives. According to Ladner et al. (US 2016/0039788 A1), a compound having the structure of:
PNG
media_image36.png
142
340
media_image36.png
Greyscale
(see e.g., [0198]), is an exemplary compound of formula (I)
PNG
media_image37.png
52
137
media_image37.png
Greyscale
useful for inhibit deoxyuridine triphosphatase (dUTPase), a ubiquitous enzyme that is essential for viability in both prokaryotic and eukaryotic organisms (see e.g., [0005];[0008]), wherein
PNG
media_image38.png
41
40
media_image38.png
Greyscale
is a uracil isostere selected from:
PNG
media_image39.png
105
116
media_image39.png
Greyscale
, wherein W is a bond or optionally substituted -CH2-; X is, inter alia, a divalent optionally substituted C6-C10 aromatic hydrocarbon group (see e.g., [0148]-[0149]); and the term “optionally substituted” refers to, inter alia, halo including fluoro (see e.g., [0120];[0091]). In other words, the compound of formula (I) of Ladner et al., including compound composed of
PNG
media_image39.png
105
116
media_image39.png
Greyscale
directly link to a C6-C10 aromatic hydrocarbon group, such as phenyl, that can be optionally substituted with fluoro, are taught to have dUTPase inhibiting effect rather than engaging with any E3 ubiquitin ligase, binding to any protein of interest, and degrading any protein. Therefore, it is not apparent that this common structure feature circled as follows:
PNG
media_image40.png
123
462
media_image40.png
Greyscale
shared among all the compound species of Formula (II) contributes to the substantial feature essential for the compound to have the desired property of engaging with any E3 ubiquitin ligase, binding to any protein of interest, and degrading any protein.
Additionally, the Markush grouping of compound of Formula (I) includes wide variety of Linker, which includes the alternated structure of
PNG
media_image41.png
72
99
media_image41.png
Greyscale
recites in claim 17, such as
PNG
media_image42.png
60
160
media_image42.png
Greyscale
and
PNG
media_image43.png
107
234
media_image43.png
Greyscale
that are structurally distinct and do not share the substantial structural similarity. It is further noted that the Linker is composed of wide variety of L1, L2, L3 and
PNG
media_image41.png
72
99
media_image41.png
Greyscale
that belongs to different chemical or physical classes, for instance, instant claim 9 recites L1 includes -O- (a heteroarom), -C1-8alkylene- (an aliphatic hydrocarbon) and
PNG
media_image44.png
75
130
media_image44.png
Greyscale
(a ring), and they are not known in the art to belong to the same chemical class. It is also not apparent that the presence of any additional atom(s) in addition to glutarimide constitutes a substantial structure feature for the compound of formula (I) as a whole for the desired property of engaging with any E3 ubiquitin ligase, binding to any protein of interest, and degrading any protein.
Furthermore, the Markush grouping of compound of Formula (I) includes wide variety of Warhead, encompassing any targeting moiety that binds to any target protein. In the present case, the alternated Warhead including those having the formula:
PNG
media_image45.png
217
191
media_image45.png
Greyscale
. According to Liu et al. (WO 2021/160087 A1; WIPO counterpart to US 2023/0131025 A1), a compound J-018 having the structure of:
PNG
media_image46.png
192
458
media_image46.png
Greyscale
(see e.g., [0390]) is an exemplary compound of Formula (I) useful as an EGFR inhibitor (see e.g., [0005]). While the compound J-018 of Liu et al. share the same common structure feature circled as follows:
PNG
media_image47.png
212
170
media_image47.png
Greyscale
, said compound is taught have EGFR inhibiting effect rather than inhibiting all and any target protein. Therefore, it is not apparent that the presence of the common structure feature noted above constitutes a substantial structure feature for the compound of formula (I) as a whole for the desired property of engaging with any E3 ubiquitin ligase, binding to any protein of interest, and degrading any protein. In addition, instant claim 18 recites a group of alternaetd Warhead, including any moeity that binds to any receptors, any enzyme and any proteins invovled in vast variety of different acitiviteis, including transferase activity and isomerase activity. In other words, these alternated Warhead moeities do not share the same common use as these alternated species do not bind to the same receptor, enzyme or protien as a target. Same logic applies to instant claim 19, which recites a group of alternaetd Warhead, including any moeity that binds to vast variety of different target protein, including dopamine receptors, HIV 1 integrase, sodium channel. Therefore, these alternated Warhead moeities also do not share the same common use.
Each of these findings demonstrates that not all members recited in this Markush grouping belong to the same recognized chemical class; i.e., the species fail to share a single structural similarity or any substantial structural feature. Additionally, the alternated compound species of formula (I) embraced by the instant claims fail to share a single structural similarity or a common use that flows from the substantial structural feature for the reasons set forth above.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
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 and 3-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry Number 1267777-90-1 (Entered on STN Registry on March 10, 2011).
CAS Registry Number 1267777-90-1 from STN database teaches a compound having the structure of:
PNG
media_image48.png
338
427
media_image48.png
Greyscale
.
Said compound is a compound of Formula (I):
PNG
media_image49.png
111
514
media_image49.png
Greyscale
, wherein s1 is 0; s2 is 0; and Z1, Z2, and Z4 are CRZ, and RZ, at each occurrence, is hydrogen; and R1 is fluoro; and R2 is chloro.
Therefore, the claimed invention is being anticipated by CAS Registry Number 1267777-90-1.
Claim Rejections - 35 USC § 103
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 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, 3-14, 17-20 and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO 2021/036922 A1, cited in the IDS filed on December 30, 2024; WIPO counterpart to US 2022/0306659 A1, cited in PTO-892), in view of Phillips et al. (WO 2017/197046 A1; cited in the IDS filed on October 23, 2025).
Please note Zhao-WO, published in Chinese, is the WIPO counterpart to US 2022/0306659 A1 ("Zhao-US"). Zhao-US is available as prior art under 35 USC § 102(a)(2) as a results of its publication date of September 29, 2022. Zhao-WO written in Chinese is a prior art under 35 USC § 102 (a)(1) as a result of its March 4, 2021 publication date. Because Zhao-US, which is the continuing chain of Zhao-WO, appears to have identical disclosures as Zhao-WO, any reference hereinafter to column and line numbers will be based upon the US patent disclosure. Such reference should be interpreted as corresponding to the disclosure of the aforementioned WO counterpart.
Zhao et al. teaches inducing the degradation of Epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) through the intracellular ubiquitin-proteasome pathway provides a new idea for the treatment of cancer (see e.g., [0007]); and a compound C285, 3-(4-(5-(4-(1-(4-((5-bromo-4-((5- (dimethylphosphoryl)quinoxalin-6-yl)amino)pyrimi-din-2-yl)amino)-5-methoxy-2-methylphenyl)piperi- din-4-yl)piperazin-1-yl)pentyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, having the structure of:
PNG
media_image50.png
39
47
media_image50.png
Greyscale
is an exemplary compound of general formula (X) and general formula (I) useful for inhibiting or inducing the degradation of EGFR and ALK (see e.g., [0945]; [0002]; claim 28). Zhao et al. further teaches the compound of formula (I)
PNG
media_image51.png
204
348
media_image51.png
Greyscale
or a pharmaceutically acceptable salt, enantiomer, diastereomer, racemate, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or mixture thereof has the structure of the following formulas, inter alia,
PNG
media_image52.png
298
362
media_image52.png
Greyscale
and
PNG
media_image53.png
326
349
media_image53.png
Greyscale
(see e.g., [0340]), wherein
PNG
media_image54.png
21
31
media_image54.png
Greyscale
represents that the point of attachment to the rest of the molecule can be located at the available point of the ring (see e.g., [0128]); Rw is, inter alia, hydrogen or halogen; Rs1 is selected from, inter alia, halogen; and s1 is 0, 1, 2, or 3 (see e.g., claim 1). Zhao et al. further teaches the term “halogen” refers to, inter alia, fluorine (see e.g., [0085]); Z5 is CRZ5 (see e.g., [0265]); RZ5 is, inter alia, H (see e.g., [0280]); R4 is C1-6 alkyl; X is -C(Rx)=, wherein Rx and R8 are taken together with the C atoms to which they are attached to form 5- to 6-membered heteroaryl; the and the groups containing, inter alia, heteroaryl are each optionally substituted with 1, 2, 3 or more Rs, wherein Rs is independently selected from, inter alia, C1-6 alkyl (see e.g., claim 1). Zhao et al. further teaches a pharmaceutical composition, comprising: the compound, or the pharmaceutically acceptable salt, enantiomer, diastereomer, racemate, solvate, hydrate, polymorph, prodrug or isotopic variant thereof and pharmaceutically acceptable excipient(s)(see e.g., claim 29).
Zhao et al. does not expressly teach
PNG
media_image55.png
96
122
media_image55.png
Greyscale
.
Phillips et al. teaches compounds that causes degradation of a selected protein via the ubiquitin-proteasome pathway (p. 6, line 10-11); and further teaches C3-carbon substituted-glutarimides and analogues thereof, also referred to therein as “Degrons”, can bind to an E3 ligase (typically the cereblon protein). Phillips et al. further teaches compound of Formula I, II, V and VI includes a target ligand that binds to a selected targeted protein, a “Degron” which binds to an E3 Ligase, and optionally a Linker that covalently links the Targeting Ligand to the Degron (see e.g., p. 6, line 10-13); wherein the Target Protein is selected from, inter alia, EGFR (see e.g., p. 160, line 26-27). Philips et al. further teaches a compound 63 having the structure of:
PNG
media_image56.png
95
132
media_image56.png
Greyscale
(see e.g., p. 350, Scheme 48) is an exemplary degron having Kd of 10-50 μM in the cell viability analysis (see e.g., Example 8; Table 1).
According to MPEP 2144.09 I, “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. ‘An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.’ In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979)”. In the present case, the difference between the compound C285 of Zhao et al. and the claimed invention is that the prior art compound contains isoindolinone (
PNG
media_image57.png
200
400
media_image57.png
Greyscale
) rather than 2,6-difluorobenzene (
PNG
media_image58.png
200
400
media_image58.png
Greyscale
) instantly claimed, and contains a linker attached to a different carbon position of the phenyl ring shown below (see shaded):
PNG
media_image59.png
751
539
media_image59.png
Greyscale
; However, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting Compound 285 of Zhao et al., and then modify said compound 285 by substituting the isoindolinone with a 2,6-difluorophenyl and attached the linker at the 4 position of the phenyl ring (see shaded
PNG
media_image60.png
93
81
media_image60.png
Greyscale
) as taught by Zhao et al. One would have been motivated to do so, because Philips et al. teaches compound 63 having the structure of
PNG
media_image56.png
95
132
media_image56.png
Greyscale
is an exemplary degrons that can be link to a Targeting Ligand, including EGFR Targeting Ligand, to degrade protein via the ubiquitin proteasome pathway; and Zhao et al. teaches the compound of formula (I) is useful for degrading EGFR or ALK through intracellular ubiquitin-proteasome pathway, and the
PNG
media_image61.png
116
190
media_image61.png
Greyscale
of compound of formula (I) includes
PNG
media_image62.png
114
186
media_image62.png
Greyscale
, wherein
PNG
media_image54.png
21
31
media_image54.png
Greyscale
represents that the point of attachment to the rest of the molecule can be located at the available point of the ring; Z5 includes CH; Rw includes halogen such as fluoro; Rs1 includes halogen such as fluoro; and S1 includes 1. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting isoindolinone with phenyl of Philips et al. would have successfully arrive at the
PNG
media_image61.png
116
190
media_image61.png
Greyscale
moiety useful for binding to an E3 ligase, and by substituting said phenyl with 2 fluoro atoms as halogens at Rw and Rs1 and attached linker at any position of said bifluorophenyl in accordance to the Formula (I) of Zhao et al., including the 2 and 6 position (
PNG
media_image58.png
200
400
media_image58.png
Greyscale
) and a linker attached to the 4 position of phenyl, would have successfully arrive at the compound of general formula (I) of Zhao et al. useful for inhibiting or inducing the degradation of EGFR or ALK; and said compound with a pharmaceutically acceptable excipient would successfully arrive at a pharmaceutical composition; and that also renders obvious the limitation of “wherein Warhead is a moiety which binds to a target protein, wherein said protein is… proteins with kinase activity” in claim 18 and “wherein Warhead is a moiety which binds to a target protein, wherein said target protein is…EGF receptor tyrosine kinase” in claim 19.
Please note the expanded compound species set forth above is a compound of Formula (I):
PNG
media_image63.png
104
482
media_image63.png
Greyscale
, wherein s1 is 1; s2 is 1;
PNG
media_image25.png
63
59
media_image25.png
Greyscale
is
PNG
media_image1.png
11
1
media_image1.png
Greyscale
; R1 and R2 are each independently fluoro (halogen); Linker is
PNG
media_image64.png
82
272
media_image64.png
Greyscale
having the structure of:
PNG
media_image65.png
43
207
media_image65.png
Greyscale
; and warhead is
PNG
media_image66.png
218
193
media_image66.png
Greyscale
having the structure of:
PNG
media_image50.png
39
47
media_image50.png
Greyscale
. Please note the fact that Zhao et al. teaches the compound of formula (I) is a racemate, it renders obvious the limitation of “
PNG
media_image67.png
116
151
media_image67.png
Greyscale
” instantly claimed.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 1, 3-14, 17-20 and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO 2021/036922 A1; WIPO counterpart to US 2022/0306659 A1), in view of Phillips et al. (WO 2017/197046 A1) as applied to claims 1, 3-14, 17-20 and 88 above, and further in view of Liu et al. (WO 2021/160087 A1; WIPO counterpart to US 2023/0131025 A1).
To the extent that the claimed invention is drawn to the elected species of compound of Formula (I), then the following 35 U.S.C. 103 rejection applies.
Please note Liu-WO, published in Chinese, is the WIPO counterpart to US 2023/0131025 A1 ("Liu-US"). Liu-US is available as prior art under 35 USC § 102(a)(2) as a results of its publication date of April 27, 2023. Liu-WO written in Chinese is a prior art under 35 USC § 102 (a)(2) as a result of its August 19, 2021 publication date. Because Liu-US, which is the continuing chain of Liu-WO, appears to have identical disclosures as Liu-WO, any reference hereinafter to column and line numbers will be based upon the US patent disclosure. Such reference should be interpreted as corresponding to the disclosure of the aforementioned WO counterpart.
The teachings of Zhao et al. and Phillips et al. are set forth above and applied as before.
Zhao et al. and Phillips et al. does not expressly teach the elected species of compound of Formula (I); However, Zhao et al. further teaches the compound of formula (I) has the structure of the following formulas, inter alia,
PNG
media_image53.png
326
349
media_image53.png
Greyscale
(see e.g., [0340]); in a specific embodiment, L1 is bond (see e.g., [0283]); L2 is, inter alia, -CH2CH2- or -C(O)- (see e.g., [0531]); E is selected from, inter alia, -CH2CH2CH2-, and
PNG
media_image68.png
110
65
media_image68.png
Greyscale
(see e.g., [0534]); m is 1 (see e.g., [0294]);
PNG
media_image69.png
17
18
media_image69.png
Greyscale
represents the point of attachment (see e.g., [0495]).
Liu et al. teaches a compound J-018 having the structure of:
PNG
media_image46.png
192
458
media_image46.png
Greyscale
(see e.g., [0390]) is an exemplary compound of Formula (I) useful as an EGFR inhibitor (see e.g., [0005]). Liu et al. further teaches the compound of Formula (I):
PNG
media_image70.png
161
329
media_image70.png
Greyscale
, R is interpedently selected from the group consisting of, inter alia, -CH2CH3 and
PNG
media_image71.png
75
63
media_image71.png
Greyscale
(see e.g., claims 1 and 4).
In the present case, the difference between the modified compound C285 of Zhao et al. and Phillips et al. set forth above and the elected compound species is that the modified compound C285 contains -CH2CH2CH2CH2CH2- rather than
PNG
media_image72.png
71
60
media_image72.png
Greyscale
, and contains the
PNG
media_image50.png
39
47
media_image50.png
Greyscale
moiety rather than
PNG
media_image1.png
11
1
media_image1.png
Greyscale
instantly claimed shown below:
PNG
media_image73.png
805
668
media_image73.png
Greyscale
However, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by further modifying the modified compound C285 of Zhao et al. and Phillips et al. set forth above by substituting the -CH2CH2CH2CH2CH2- with
PNG
media_image72.png
71
60
media_image72.png
Greyscale
, and
PNG
media_image50.png
39
47
media_image50.png
Greyscale
with
PNG
media_image1.png
11
1
media_image1.png
Greyscale
. One would have been motivated to do so, because Zhao et al. teaches compounds of formula (I), including formula (I-1-E) employed the ubiquitin-proteasome system to induce degradation of EGFR or ALK, and teaches the linker moiety -L1-(E)m-L2- of these formulae includes E having the structure of
PNG
media_image68.png
110
65
media_image68.png
Greyscale
; L1 is bond; L2 is -C(O)-; m is 1; Phillips et al. teaches compounds that causes degradation of a selected protein via the ubiquitin-proteasome pathway composed of C3-carbon substituted-glutarimides and analogues thereof that bind to an E3 ligase, a target ligand that binds to a selected targeted protein, including EGFR, and a linker that covalently links the two; and Liu et al. teaches compound J-018 is an EGFR inhibitor and an exemplary compound of formula (I), and further teaches the compound of formula (I) can have -CH2CH3 or
PNG
media_image71.png
75
63
media_image71.png
Greyscale
as R substitute on the quinoline ring. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the EGFR target moiety for another, substituting
PNG
media_image50.png
39
47
media_image50.png
Greyscale
with
PNG
media_image1.png
11
1
media_image1.png
Greyscale
, which is compound J-018 of Liu et al. (
PNG
media_image46.png
192
458
media_image46.png
Greyscale
) that replaces
PNG
media_image71.png
75
63
media_image71.png
Greyscale
with -CH2CH3 at R; and by substituting one linker for another, substituting -CH2CH2CH2CH2CH2- with
PNG
media_image72.png
71
60
media_image72.png
Greyscale
, which is -L1-(E)m-L2-, wherein L1 is bond; L2 is -C(O)-; m is 1; and E is
PNG
media_image68.png
110
65
media_image68.png
Greyscale
, would have successfully arrive a compound useful for degrading EGFR or ALK through the intracellular ubiquitin-proteasome pathway.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-14, 17-20, and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 8, 11, 14, 16, 20, 22, 23, 26, 30-34, 44, 47-50, and 53-56 of copending Application No. 18/015,561 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application is drawn to compounds of Formula (I) that overlaps with the compounds of Formula (I) instantly claimed. Specifically, the claims of the reference application recites a compound of Example 489 having the structure of:
PNG
media_image74.png
214
306
media_image74.png
Greyscale
(see e.g., claim 47), which is also a compound of Formula (I) (see e.g., claim 1); and a pharmacetuical compspotion comprising the compound or a pharmacetuically acceptable salt, stereoisomer, or tautomer thereof, together with a pharmaceutically acceptable excipient (see e.g., claim 48).
Therefore, the claimed invention is being anticipated by the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-14, 17-20, and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, 12, 17, 20-21, 27, 29, 31-34, 40, 46, 47, 49, and 50 of copending Application No. 18/016,292 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application is drawn to compounds of Formula (I) that overlaps with the compounds of Formula (I) instantly claimed. Specifically, the claims of the reference application recites a compound of Example 515 having the structure of:
PNG
media_image75.png
202
380
media_image75.png
Greyscale
(see e.g., claim 49), which is also a compound of Formula (I) (see e.g., claim 1). The claims of the reference application is further drawn to the stereoisomer of the compound (see e.g., claim 1), and a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, together with a pharmaceutically acceptable excipient (see e.g., claim 50).
Therefore, the claimed invention is being anticipated by the reference application; and the elected compound species is obvious in view of the reference application based on the fact that the compound of Example 515 includes stereoisomer thereof.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-14, 17-20, and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 8, 9, 11-17, 19-32, 35-37, 39, 41, and 45-47 of copending Application No. 18/264,881 (reference application), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) and Zhao et al. (WO 2021/036922 A1, cited in the IDS filed on December 30, 2024; WIPO counterpart to US 2022/0306659 A1, cited in PTO-892).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of reference application is drawn to a compound of Formula (X) that overlaps in scope, specifically, the claim(s) pertains to a compound having the structure of:
PNG
media_image76.png
41
21
media_image76.png
Greyscale
(see e.g., claim 39)(referred to herein as “Compound 20”). The claims of reference application further teaches the compound of Formula (X):
PNG
media_image77.png
256
566
media_image77.png
Greyscale
or a stereoisomer thereof useful for decreasing EGFR activity (see e.g., claim 41), wherein Z7 is -CR9 and N; Z5 is selected from, inter alia, -CR2; Z6 is selected from, inter alia, -CR3; R2 and R3 together with the carbon atoms to which they are attached, form a 5-6 membered saturated or partially or completely unsaturated ring, said ring comprising 0-3 heteroatoms independently selected from, inter alia, nitrogen; said ring is optionally substituted with at least one substituent R2e; R2e is independently, inter alia, -C1-8 alkyl (see e.g., claim 1);
PNG
media_image78.png
93
249
media_image78.png
Greyscale
is, inter alia,
PNG
media_image79.png
78
169
media_image79.png
Greyscale
and
PNG
media_image80.png
51
190
media_image80.png
Greyscale
(see e.g., claim 31); degron is selected from, inter alia,
PNG
media_image81.png
83
123
media_image81.png
Greyscale
(see e.g., claim 35); wherein
PNG
media_image82.png
124
129
media_image82.png
Greyscale
is
PNG
media_image83.png
183
210
media_image83.png
Greyscale
or
PNG
media_image84.png
193
187
media_image84.png
Greyscale
(see e.g., claim 47).
Zhao et al. teaches a pharmaceutical composition, comprising: a compound, or a pharmaceutically acceptable salt, enantiomer, diastereomer, racemate, solvate, hydrate, polymorph, prodrug or isotopic variant thereof and pharmaceutically acceptable excipient(s)(see e.g., claim 29); wherein the compound is a compound of formula (I), including
PNG
media_image53.png
326
349
media_image53.png
Greyscale
(see e.g., [0340]) useful for inhibiting or inducing the degradation of EGFR and ALK (see e.g., [0945]; [0002]; claim 28).
The reference application does not teach
PNG
media_image1.png
11
1
media_image1.png
Greyscale
. The reference application also does not teach a pharmaceutically acceptable excipient.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for
the rational modification of lead compounds into safer and more clinically effective agents (see e.g.,
“introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar
biological activity, and have been classified as either classical or nonclassical, wherein the classical
bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and
Erlenmeyer’s definition of isosteres (see e.g., p. 3148-3149). Patani et al. further teaches benzene and pyridine are classical isosteric substitutions resulted in analogues with retention of biological activity within different series of pharmacological agent (see e.g., p. 3158, left column, “E. Ring Equivalents”, 1st paragraph).
In the present case, the difference between the compound 20 of reference application and the elected compound species is that the reference application contains
PNG
media_image79.png
78
169
media_image79.png
Greyscale
rather than
PNG
media_image80.png
51
190
media_image80.png
Greyscale
, contains
PNG
media_image85.png
114
118
media_image85.png
Greyscale
rather than
PNG
media_image1.png
11
1
media_image1.png
Greyscale
, and contains
PNG
media_image76.png
41
21
media_image76.png
Greyscale
rather than
PNG
media_image81.png
83
123
media_image81.png
Greyscale
shown below (see shaded):
PNG
media_image86.png
543
449
media_image86.png
Greyscale
.
However, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the Compound 20 of reference application, and then modify said compound by replacing
PNG
media_image79.png
78
169
media_image79.png
Greyscale
with
PNG
media_image80.png
51
190
media_image80.png
Greyscale
, replacing
PNG
media_image76.png
41
21
media_image76.png
Greyscale
with
PNG
media_image81.png
83
123
media_image81.png
Greyscale
, and then replacing the pyridine of
PNG
media_image85.png
114
118
media_image85.png
Greyscale
with a benzene ring as taught by Patani et al., and the benzene of
PNG
media_image85.png
114
118
media_image85.png
Greyscale
with a pyridine, and then substituted the pyridine with -C1-8 alkyl as taught by the reference application. One would have been motivated to do so, because the reference application teaches the
PNG
media_image78.png
93
249
media_image78.png
Greyscale
of Formula (I) includes
PNG
media_image79.png
78
169
media_image79.png
Greyscale
and
PNG
media_image80.png
51
190
media_image80.png
Greyscale
; the degron of Formula (I) includes
PNG
media_image81.png
83
123
media_image81.png
Greyscale
; and the
PNG
media_image87.png
119
126
media_image87.png
Greyscale
moiety of Formula (I) includes
PNG
media_image83.png
183
210
media_image83.png
Greyscale
and
PNG
media_image84.png
193
187
media_image84.png
Greyscale
, where R2e includes -C1-8 alkyl; and Patani et al. teaches benzene and pyridine are classical isosteric substitutions resulted in analogues with retention of biological activity. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by modifying the pyridine ring of
PNG
media_image85.png
114
118
media_image85.png
Greyscale
of Compound 20 with a benzene ring taught by Patani et al., and then further modifying the compound 20 in accordance with the formula (I) of reference application addressed above would have successfully arrive at a compound similar to compound 20 useful for decreasing EGFR activity.
Regarding claim 88, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine the modified compound 20 of reference application and Patani et al. set forth above with a pharmaceutically acceptable excipient taught by Zhao et al., because Zhao et al. teaches the compound useful for inhibiting or inducing EGFR degradation with a pharmaceutically acceptable excipient can arrive at a pharmaceutical composition. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the modified compound 20 of reference application and Patani et al. capable of decreasing EGFR activity can successfully combine with a pharmaceutically acceptable excipient to arrive at a pharmaceutical composition suitable for administration.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-14, 17-20, and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 12-14, 18-19, 22, 23, 24-26 and 28-29 of copending Application No. 18/771,529 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of reference application is drawn to a compound of Formula (X) that overlaps in scope, specifically, the claim(s) pertains to a compound having the structure of:
PNG
media_image88.png
207
320
media_image88.png
Greyscale
(see e.g., claim 23)(referred to herein as “Compound 10”); and is a compound of Formula (I):
PNG
media_image89.png
255
346
media_image89.png
Greyscale
useful for treating a disease that can be affected by EGFR modulation (see claim 25), wherein degron is
PNG
media_image90.png
84
14
media_image90.png
Greyscale
(see e.g., claim 1); wherein the
PNG
media_image91.png
47
206
media_image91.png
Greyscale
moiety is
PNG
media_image92.png
50
198
media_image92.png
Greyscale
, or
PNG
media_image93.png
112
236
media_image93.png
Greyscale
(see e.g., claim 22). The claims of reference application is further drawn to a pharmaceutical composition comprising the compound together with a pharmaceutically acceptable excipient (see e.g., claim 24).
The difference between the compound 10 of reference application and the elected compound species is that the reference application contains
PNG
media_image92.png
50
198
media_image92.png
Greyscale
rather than
PNG
media_image79.png
78
169
media_image79.png
Greyscale
; and contains
PNG
media_image90.png
84
14
media_image90.png
Greyscale
rather than
PNG
media_image90.png
84
14
media_image90.png
Greyscale
shown below (see shaded):
PNG
media_image94.png
525
415
media_image94.png
Greyscale
.
According to MPEP 2144.09 II, “[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)”. It would have been prima facie obvious to one of oridnary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the Compound 10 of reference application, and then modify said compound by replacing
PNG
media_image90.png
84
14
media_image90.png
Greyscale
with
PNG
media_image90.png
84
14
media_image90.png
Greyscale
, then replacing
PNG
media_image92.png
50
198
media_image92.png
Greyscale
with
PNG
media_image93.png
112
236
media_image93.png
Greyscale
, and then adding additional carbon ring atom to the azetidine to give pyrrolidine. One would have been motivated to do so, because the reference application teaches the
PNG
media_image91.png
47
206
media_image91.png
Greyscale
of Formula (I) includes
PNG
media_image92.png
50
198
media_image92.png
Greyscale
and
PNG
media_image93.png
112
236
media_image93.png
Greyscale
; the degron of Formula (I) includes
PNG
media_image90.png
84
14
media_image90.png
Greyscale
. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by modifying the degron and
PNG
media_image91.png
47
206
media_image91.png
Greyscale
of Compound 10 in accordance with the formula (I) of reference application addressed above would have successfully arrive at a compound similar to compound 10 useful for treating a disease that can be affected by EGFR modulation; and by addiing additional ring atom to the azetidine ring of
PNG
media_image93.png
112
236
media_image93.png
Greyscale
would have succesfully arrive a homog with similar utility. Please note according to MPEP 2144.09 III “[p]rior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979)”.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights