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 .
Information Disclosure Statement
Three information disclosure statement (IDS) submitted: one on 04/05/2023; one on 09/12/2024; and one on 04/03/2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The use of the term CellTiter-Glo®, for example, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
While the Examiner has made every attempt to check the Specification for trade mark compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding trade mark use compliance.
The disclosure is objected to because of the following informalities: The unit of mass “daltons” should be lower case.
Appropriate correction is required.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-3, 30-31, 40-43, 47-49, 53-55, 58-60, 63 and 76-78), in the reply filed on 01/09/2026 is acknowledged.
In response to the election requirement, Applicant has elected:
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For E3ULB-C1-L1 and E3ULB2-C3-L3, the elected compounds were found to be free of the art, therefore, the search was expanded to encompass any aromatic 1,2-diol linker (for L1 and L3). Furthermore, for the purposes of applying art, the elected E3ULB-C1-L1 will be considered as being interchangeable with E3ULB2-C3-L3 in the claimed therapeutic compositions. Similarly, the elected TPB-C2-L2 and TPB2-C4-L4 will be considered as being interchangeable in the claimed compositions.
Claims 47-49, 53-54, 60, 63 and 79-80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/09/2026.
Status of the Claims
Claims 1-3, 30-31, 40-43, 47-49, 53-55, 58-60, 63 and 76-80 are pending in this application. Claims 4-29, 32-39, 44-46, 50-52, 56-57, 61-62, 64-75, 81-82 have been cancelled by applicant. Claims 1-3, 30-31, 40-43, 55, 58-59, and 76-80 are under consideration herein. Claims 47-49, 53-54, 60, 63, and 79-80 are withdrawn from consideration.
Claim Objections
Claims 1-2 and 76-78 is objected to because of the following informalities:
In claims 1 and 76-78, the term “Daltons” after “420 Daltons” should be lower case.
In claim 2, the “is” after “boronic ester-containing compound” in line 12, should be removed.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 2-3, 30-31, 40-43 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 2 is indefinite because in the limitations: “when R1 to R4 are adjacent they may optionally be …” or “-C2-TPB, or can be …” or “R5 to R7 are adjacent they may optionally …” The terms “may be” or “can be” raise a question as to whether the limitations are or aren’t. Examiner suggests rewording to read: “when R1 to R4 are adjacent they are optionally …” or “-C2-TPB, or is/are …” or “R5 to R7 are adjacent they are optionally …”
Claim 3 is rejected for depending upon the limitations of claim 2.
Claim 30 is indefinite because in the limitations: “when R1 to R4 can independently be …” The term “can be” raises a question as to whether the limitations is or isn’t. Examiner suggests rewording to read: “when R1 to R4 are independently …”
Claim 31 is rejected for depending upon the limitations of claim 30.
Claim 40 is indefinite because, for instance, only 1 R1 group is present on X1 – when X1 is C and R1 is H, for example, the carbon will be missing two additional hydrogens to complete full valency. The same issue is present with X2-R2 and X3-R3.
Claims 41-43 are rejected for depending upon the limitations of claim 40.
Claim 43 is indefinite because, when X1 is C, for example, and R1 comprises a bond to -C2-L2, for example, the carbon will be missing two additional hydrogens to complete full valency.
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.
Claims 1-2, 30-31, 40, 55, 58-59, and 76-78 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (WO 2019/152440 A1) (“Zhou”); and Arnold et al. (US 2014/0243286 A1) (“Arnold”).
Regarding claims 1, 55, 58-59 and 76-78, Zhou discloses their compounds A-L-B of Formula I, wherein A (corresponding to instant L1 and/or L3) is a BRD9 binding moiety, L (corresponding to instant C1 and/or C3) is a linker, and B is a degradation moiety (corresponding to instant E3ULB and/or E3ULB2) (page 5, lines 12-end). Zhou teaches their compounds may be administered in combination with additional therapeutic agents, such as other agents that treat cancer (page 57, lines 23-25).
Zhou teaches their B (degradation element) can have the structures 2a or 1a below (reading on elected E3ULB and/or E3ULB2) (page 6, bottom; and page 180, bottom).
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Zhou discloses their linker has Formula II below (page 8), wherein f-k can be 0 or 1; A1 can be a bond to A and A2 is a bond to B; B1-4 are C1-2 alkyl, optionally substituted with -C-, -S-, -NH-, etc.; C1-2 can be -C(O)-; and D can be alkyl; with some preferred embodiments having the structures II-a-c below (page 9).
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Zhou discloses their A BRD9 binding moiety can have the structure E-a below, wherein R22-23 can be H, alkyl, etc.; R24 can be halogen, alkyl, etc.; R25 can be alkyl, hydroxyl, amino, etc.; and s and s’ can be 0, 1, 2, etc. (page 9, bottom).
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Zhou specifically discloses the compound D10 below as a preferred embodiment – labeled with the instantly used labels for clarity (page 39, bottom). The linker element corresponding to instant L1/L3 has a MW of about 296, also reading on the claimed range of 54-420 daltons. While Zhou does not specifically disclose an embodiment in which their group corresponding to instant L1/L3 is an aromatic diol (as in the elected species), Zhou teaches 1,2 methoxy-phenyl group in the compound below and discloses that in their Formula E-a- (which corresponds to instant L1/L3 in their Formula A-L-B) R25 may be hydroxy and s may be 2. Regarding instantly elected species E3ULB-C1-L1, while Zhou does not disclose any specific embodiments comprising their 2a element above as B in Zhou’s A-L-B, Zhou specifically discloses their B group (corresponding to instant E3ULB) may be Formula 2a (shown above). Thus, Zhou discloses a relatively narrow subgenus, encompassed by the broad genus of the instant claims, which encompasses the instantly elected species.
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Therefore, regarding the instant compounds elected as E3ULB-C1-L1 and/or E3ULB2-C3-L3 in instant claims 1, 55, 58-59, and 76-78, one having ordinary skill in the art would have found the instant compounds prima facie obvious, since they are generically embraced by Zhou’s disclosed formulae and preferred embodiments; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of cancer therapeutic compounds disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
Further regarding claims 55 and 58-59, Zhou’s compound above reads on the at least the compounds below, for the reasons outlined above.
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and
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and
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Regarding the limitations “wherein E3ULB is an E3 ligase binding moiety” or “wherein the E3ULB binds to the CRBN subunit of the CULLIN4A or CULLIN4B” in claims 1, 55, and 58, Applicant is advised that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02.
While Zhou does not teach the instantly elected TBP-C2-L2 or TBP2-C4-L4 in a composition with their compounds; the teachings of Arnold are relied upon for these disclosures.
Arnold discloses that current drug design has not addressed the need for therapies that interact with multiple areas/domains of biomolecules ([0002]). Arnold discloses monomers capable of forming a multimer with other monomers in vivo, allowing for modulation of one or more biomolecules substantially simultaneously ([0006]). Arnold teaches their bromodomain modulators are useful for diseases related to malignant cell activation and proliferation (reading on cancer – which is the same intended use of Muller’s and the instant invention) ([0004]). Arnold discloses the elected compounds 1, 59, and 65 below (pages 200, 201 and 312), which anticipate/read on the instantly elected TBP-C2-L2 (Applicant is reminded that elected TBP-C2-L2 and TBP2-C4-L4 species are being treated as being interchangeable in the claimed compositions, as they are all encompassed by the limitations of instant claim 1).
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While elected compound TBP2-C4-L4 is not disclosed exactly, Arnold discloses the constitutional isomers 59 and 65 above, which render the instant elected compound obvious. Specifically, 59 differs only because the boronic acid is para- to the amide (vs meta- in elected compound). For compound 65, the nitrogen and carbonyl of the amide meta- to the phenyl boronic acid are inverted. However, Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Therefore, regarding claims 1, 40, 55, 58-59 and 76-78, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to prepare a therapeutic composition comprising one or two of Zhou’s compounds, further comprising one or two of Arnold’s compounds. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Zhou discloses their compounds as BRD9 inhibitors for the treatment of cancers, and teaches that their BRD9 inhibitors may be administered alone or in combination with other anticancer treatments; further because Arnold discloses their monomers, intended for combination with BRD9 therapeutics (such as Zhou’s) for the preparation of multimers in vivo, for the treatment of proliferative diseases, such as cancer.
Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two or more agents.
Regarding claim 2, Zhou discloses their compounds corresponding to instant E3ULB-C1-L1 and E3ULB2-C3-L3, wherein their group corresponding to instant L1 reads on the instant claim when instant R4 binds to -C1-E3ULB; R2 is heteroaryl; and R1,3 are H. Arnold discloses their compounds corresponding to instant TBP-C2-L2 and TBP2-C4-L4, wherein their group corresponding to instant L2 is derived from an aromatic boronic acid containing compound
Regarding claims 30-31, Zhou discloses their L (corresponding to instant C1 and C3) can have the structure II-c above, which read on instant
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when m is 1. While the instantly disclosed preferred embodiment of L shows a methylene between -NH- and Z1, Zhou teaches that in their linkers of Formula II, g, h, i, j, and k can be 0; leaving A1-B1-D-A2, wherein A1 (corresponding to Z2) can be a bond to B (which corresponds to instant E3ULB/E3ULB2) and A2 (corresponding to Z1) is a bond to A (which corresponds to instant L1); B1 can be N; and D can be -CH2-. Therefore, one having ordinary skill in the art would have found the claimed C1 “connectors” prima facie obvious, since they are generically embraced by Zhou’s disclosed formula for their linkers and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of linkers/ connectors disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is advised that compounds 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).
Claims 1-3, 30-31, 40-43, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Muller et al. (WO 2009/145899 A1) (“Muller”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”); further in view of Arnold et al. (US 2014/0243286 A1) (“Arnold”).
Regarding claims 1-3 and 55, Muller discloses their compound below in methods of treating cancer (pages 1-2) – which is the same intended use of the compounds of the instant invention. Muller teaches their compounds may be administered in combination with other therapeutic agents (para. bridging pages 3-4). Muller’s compound reads on a E3ULB-C1-L1 (presently elected as E3ULB2-C3-L3, however, as mentioned in the election/restriction section above, E3ULB-C1-L1 and E3ULB2-C3-L3 will be considered as being interchangeable).
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(page 12, top left)
While Muller does not disclose their compounds wherein the group corresponding to instant L1 is an aromatic 1,2 diol; the teachings of Meanwell are relied upon for these disclosures.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell teaches -Cl and -OH and monovalent bioisosteres (Table 1, page 2529, col. 1).
Therefore, regarding claims 1-3 and 55, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they encompass Muller’s compound in view of Meanwell. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds for the treatment of cancer disclosed by Muller, in view of Meanwell’s teaching that -Cl and -OH are classical monovalent bioisosteres, rendering their substitution for one another a routine modification in medicinal chemistry. Accordingly, one having ordinary skill in the art would have been motivated to prepare Muller’s compound wherein the -Cl’s have been replaced by ‘OH, in view of Meanwell.
Further regarding claim 55, the compound below is particularly obvious in view of Muller in view of Meanwell’s disclosure when X is O.
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While Muller in view of Meanwell do not teach the instantly elected TBP-C2-L2 in a composition with their compounds; the teachings of Arnold are relied upon for these disclosures.
Arnold discloses that current drug design has not addressed the need for therapies that interact with multiple areas/domains of biomolecules ([0002]). Arnold discloses monomers capable of forming a multimer with other monomers in vivo, allowing for modulation of one or more biomolecules substantially simultaneously ([0006]). Arnold teaches their bromodomain modulators are useful for diseases related to malignant cell activation and proliferation (reading on cancer – which is the same intended use of Muller’s and the instant invention) ([0004]). Arnold discloses the elected compounds 1, 59, and 65 below (pages 200, 201 and 312), which anticipate/read on the instantly elected TBP-C2-L2 (Applicant is reminded that elected TBP-C2-L2 and TBP2-C4-L4 species are being treated as being interchangeable in the claimed compositions, as they are all encompassed by the limitations of instant claim 1).
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While elected compound TBP2-C4-L4 is not disclosed exactly, Arnold discloses the constitutional isomers 59 and 65 above, which render the instant elected compound obvious. Specifically, 59 differs only because the boronic acid is para- to the amide (vs meta- in elected compound). For compound 65, the nitrogen and carbonyl of the amide meta- to the phenyl boronic acid are inverted. However, Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Therefore, regarding claims 1-3, 40-43, and 55, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to prepare a therapeutic composition comprising one or two of Muller’s in view of Meanwell’s compounds, further comprising one or two of Arnold’s compounds. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Muller in view of Meanwell discloses their compounds for the treatment of cancers, which may be administered alone or in combination with other anticancer treatments; further because Arnold discloses their monomers, intended for combination with other therapeutics for the preparation of multimers in vivo, for the treatment of proliferative diseases, such as cancer.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” It is therefore obvious to provide a mixture of the two or more agents.
Further regarding claim 41 and 43, the compounds below are particularly obvious in view of Muller in view of Meanwell’s disclosure:
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wherein L1 corresponds to
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Further regarding claims 41 and 43, Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding the limitations: “wherein E3ULB is an E3 ligase binding moiety” or “wherein the E3ULB binds to the CRBN subunit of the CULLIN4A or CULLIN4B” in claims 1 and 55, Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claims 30-31, Muller discloses their compound wherein the connecting element is
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Claims 1, 58-59, and 76-78 are rejected under 35 U.S.C. 103 as being unpatentable over Muller et al. (WO 2009/145899 A1) (“Muller”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”); further in view of Arnold et al. (US 2014/0243286 A1) (“Arnold”); as applied to claims 1-3, 30-31, 40-43, and 55; further in view of Zhou et al. (WO 2019/152440 A1) (“Zhou”).
The teachings of Muller, Meanwell, and Arnold are disclosed above and incorporated herein.
While Muller, Meanwell, and Arnold do not teach the instantly elected E3ULB-C1-L1 compound (interpreted as being interchangeable with E3ULB2-C3-L3); the teachings of Zhou are relied upon for these disclosures.
Zhou teaches their compounds A-L-B of Formula I, wherein A (corresponding to instant L1 and/or L3) is a BRD9 binding moiety, L (corresponding to instant C1 and/or C3) is a linker, and B is a degradation moiety (corresponding to instant E3ULB and/or E3ULB2) (page 5, lines 12-end). Zhou teaches their compounds may be administered in combination with additional therapeutic agents, such as other agents that treat cancer (page 57, lines 23-25).
Zhou teaches their B (degradation element) can have the structures 2a or 1a below (reading on elected E3ULB and/or E3ULB2 – interpreted as being interchangeable herein) (page 6, bottom; and page 180, bottom).
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Zhou discloses their linker has Formula II below (page 8), wherein f-k can be 0 or 1; A1 can be a bond to A and A2 is a bond to B; B1-4 are C1-2 alkyl, optionally substituted with -C-, -S-, -NH-, etc.; C1-2 can be -C(O)-; and D can be alkyl; with some preferred embodiments having the structures II-a-c below (page 9).
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Zhou discloses their A BRD9 binding moiety can have the structure E-a below, wherein R22-23 can be H, alkyl, etc.; R24 can be halogen, alkyl, etc.; R25 can be alkyl, hydroxyl, amino, etc.; and s and s’ can be 0, 1, 2, etc. (page 9, bottom).
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Zhou specifically discloses the compound D10 below as a preferred embodiment – labeled with the instantly used labels for clarity (page 39, bottom). The linker element corresponding to instant L1/L3 has a MW of about 296, also reading on the claimed range of 54-420 daltons. While Zhou does not specifically disclose an embodiment in which their group corresponding to instant L1/L3 is an aromatic diol (as in the elected species), Zhou teaches 1,2 dimethoxy-phenyl group in the compound below and discloses that in their Formula E-a- (which corresponds to instant L1/L3 in their Formula A-L-B) R25 may be hydroxy and s may be 2. Regarding instantly elected species E3ULB-C1-L1, while Zhou does not disclose any specific embodiments comprising their 2a element above as B in Zhou’s A-L-B, Zhou specifically discloses their B group (corresponding to instant E3ULB) may be Formula 2a (shown above). Thus, Zhou discloses a relatively narrow subgenus, encompassed by the broad genus of the instant claims, which encompasses the instantly elected species.
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Therefore, regarding the instant compounds (elected as E3ULB-C1-L1 and/or E3ULB2-C3-L3) in instant claims 1, 58-59, and 76-78, one having ordinary skill in the art would have found the instant compounds prima facie obvious, since they are generically embraced by Zhou’s disclosed formulae and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of cancer therapeutic compounds disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula.
Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
Further regarding claims 58-59, Zhou’s compound above reads on the at least the compounds below, for the reasons outlined above.
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Regarding the limitations “wherein E3ULB is an E3 ligase binding moiety” or “wherein the E3ULB binds to the CRBN subunit of the CULLIN4A or CULLIN4B” in claims 1 and 58-59, Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Further regarding claims 58-59 and 76-78, one having ordinary skill in the art would have been motivated to prepare any of the claimed compositions, with a reasonable expectation of success, because (Muller in view of Meanwell, further in view of Arnold) teach their compositions and compounds for the treatment of cancer; further because Zhou discloses their compounds, also useful for the treatment of cancer, and teaches that their compounds may be administered in combination with other chemotherapeutic agents.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two or more agents.
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, 30-31, 40-43, 55, 58-59 and 76-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 29-30, 37-40, 47-52, 54-56 of copending Application No. 18/020,025 (Copending ‘025); in view of Arnold et al. (US 2014/0243286 A1) (“Arnold”).
Regarding instant claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78, Copending ‘025 claims the instant compounds of Formula E3ULB-C1-L1 and E3ULB2-C3-L3, including the elected species below: (all claims of Copending ‘025) for the treatment of cancer.
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While Copending ‘025 does not teach the instant compounds of Formulae TBP-C2-L2 or TBP2-C4-L4 in a composition with their compounds; the teachings of Arnold are relied upon for these disclosures.
Arnold discloses that current drug design has not addressed the need for therapies that interact with multiple areas/domains of biomolecules ([0002]). Arnold discloses monomers capable of forming a multimer with other monomers in vivo, allowing for modulation of one or more biomolecules substantially simultaneously ([0006]). Arnold teaches their bromodomain modulators are useful for diseases related to malignant cell activation and proliferation (reading on cancer – which is the same intended use of Muller’s and the instant invention) ([0004]). Arnold discloses the elected compounds 1, 59, and 65 below (pages 200, 201 and 312), which anticipate/read on the instantly elected TBP-C2-L2 (Applicant is reminded that elected TBP-C2-L2 and TBP2-C4-L4 species are being treated as being interchangeable in the claimed compositions, as they are all encompassed by the limitations of instant claim 1).
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(65)
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(1)
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(59)
While elected compound TBP2-C4-L4 is not disclosed exactly, Arnold discloses the constitutional isomers 59 and 65 above, which render the instant elected compound obvious. Specifically, 59 differs only because the boronic acid is para- to the amide (vs meta- in elected compound). For compound 65, the nitrogen and carbonyl of the amide meta- to the phenyl boronic acid are inverted. However, Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Therefore, regarding instant claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78, one having ordinary skill in the art would have been motivated to prepare any of the claimed compositions, with a reasonable expectation of success, because Copending ‘025 discloses their compositions for the treatment of cancer; further because Arnold discloses their compounds, also useful for the treatment of cancer, and discloses their monomers are capable of forming a multimer with other monomers (such as Copending ‘025’s BRD inhibitors) in vivo, allowing for modulation of one or more biomolecules substantially simultaneously.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two or more agents.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 26, and 29 of copending Application No. 18/269,122 (Copending ‘122); in view of Arnold et al. (US 2014/0243286 A1) (“Arnold”).
Regarding instant claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78, Copending ‘122 claims a compound of Formula I below, reading on the instant compounds when: Degron is a E3 ubiquitin ligase, Q is a bond, R2 is -OH, and n1 is 2 (at least in Copending ‘122 claims 1, 26, and 29).
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Degron is
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or
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While Copending ‘122 does not teach the instant compounds of Formulae TBP-C2-L2 or TBP2-C4-L4 in a composition with their compounds; the teachings of Arnold are relied upon for these disclosures.
Arnold discloses that current drug design has not addressed the need for therapies that interact with multiple areas/domains of biomolecules ([0002]). Arnold discloses monomers capable of forming a multimer with other monomers in vivo, allowing for modulation of one or more biomolecules substantially simultaneously ([0006]). Arnold teaches their bromodomain modulators are useful for diseases related to malignant cell activation and proliferation (reading on cancer – which is the same intended use of Muller’s and the instant invention) ([0004]). Arnold discloses the elected compounds 1, 59, and 65 below (pages 200, 201 and 312), which anticipate/read on the instantly elected TBP-C2-L2 (Applicant is reminded that elected TBP-C2-L2 and TBP2-C4-L4 species are being treated as being interchangeable in the claimed compositions, as they are all encompassed by the limitations of instant claim 1).
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(59)
While elected compound TBP2-C4-L4 is not disclosed exactly, Arnold discloses the constitutional isomers 59 and 65 above, which render the instant elected compound obvious. Specifically, 59 differs only because the boronic acid is para- to the amide (vs meta- in elected compound). For compound 65, the nitrogen and carbonyl of the amide meta- to the phenyl boronic acid are inverted. However, Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Therefore, regarding instant claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78, one having ordinary skill in the art would have been motivated to prepare any of the claimed compositions, with a reasonable expectation of success, because Copending ‘122 discloses their compositions for the treatment of cancer; further because Arnold discloses their compounds, also useful for the treatment of cancer, and discloses their monomers are capable of forming a multimer with other monomers (such as Copending ‘122’s anticancer agents) in vivo, allowing for modulation of one or more biomolecules substantially simultaneously.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two or more agents.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 30-31, 42-55, 67-72, and 74-75 of copending Application No. 18/020011 (Copending ‘011).
Regarding instant claims 1-3, 30-31, 40-43, 55, 58-59, and 76-78, Copending ‘011 claims the compounds below, which are prepared after the combination of the instantly claimed E3ULB-C1-L1 or E3ULB2-C3-L3 with either TBP-C2-L2 or TBP2-C4-L4 (all claims of Copending ‘011). Since condensation of the diol of E3ULB-C1-L1 or E3ULB2-C3-L3 with the boronic acid of TBP-C2-L2 or TBP2-C4-L4 would be expected to happen spontaneously in the instantly claimed compositions, then Copending ‘011’s compounds read on the instant compositions. Copending ‘011 specifically claims therapeutic compositions comprising their compounds (Copending ‘011 claims 71-72) – thus anticipating the instant compositions.
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This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627