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 without traverse of Group I and Compound 10 in the reply filed on 1/5/2026 is acknowledged. Claims 85, 86, 94, 97, 98, 103, 104, 106-109 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group and species, and there being no allowable generic or linking claim.
Status of Claims
Cancelled: 1-78
Withdrawn: 85, 86, 94, 97, 98, 103, 104, 106-109
Examined Herein: 79-84, 87-93, 95, 96, 99-102, 105
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PRO 63/340,380 on 5/10/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/18/2023 and 1/14/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 5/8/2023 are accepted.
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.
Claim 79, 81, 91- 93, 95, 96, 99-101, and 103-105 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 79 recites the limitation “R2 is ring… wherein R2 is unsubstituted or is substituted with R3a, R3b, or R3c.” However, the structure of R2 is not specifically defined. Thus, when R2 is substituted, it is unclear where the substitution with R3a, R3b, or R3c takes place on the ring scaffold or how these substituents are attached thereto. As a result, the scope of R2 is unclear because, without a defined scaffold or substitution framework, the structures encompassed by substituted R2 cannot be reasonably ascertained. Further clarification is required. Dependent claims 81, 91- 93, 95, 96, 99-101, and 103-105 fall therewith.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 79-84, 87, 90, 91, 93, 95, 96, 99, and 105 are rejected under 35 U.S.C. 103 as being unpatentable over Han (US 2019/0367481 A1, Published 12/5/2019), in view of Morse (US 2018/0126013 A1, Published 5/10/2018).
With respect to claim 79, Han discloses the following compound of Formula (I), a melanocortin subtype-2 receptor (MC2R) modulator.
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[Han, 0872]
wherein:
R1 is Ra
Ra is -CH2NR8-L2-Rb
L2 is absent
Y is N,
L1 is -C(=O)-
R2 is a C6-heterocylcoalkyl
R2 is substituted with R3a and R3b
R3a is C1-fluroalkyl
R3b is -OR9
R9 is C2 alkyl
R6 is C2 alkyl
R7 is C2 alkyl
X1 is N
X2 is N
n is 0
m is 1
R4 is hydrogen. [Han, 0872]
With respect to claim 80, Hand discloses R2 is:
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. [Han, 0872]
With respect to claim 81, Han discloses R3a is -CF3, R3b is -OCH2CH3, and R3c is hydrogen. [Han, 0872]
With respect to claim 82, Han discloses R6 is -CH2CH3 and R7 is -CH2CH3. [Han, 0872]
With respect to claim 83, Han discloses the compound has the structure of Formula (VI), wherein X3 is N. [Han, 0872]
With respect to claim 84, Han discloses the compound has the structure of Formula (VIb).
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With respect to claim 87, Han discloses R3a is -CF3, R3b is -OCH2CH3, R3c is hydrogen, and R4 is hydrogen. [Han, 0872]
With respect to claim 88, Han discloses the compound of Formula (I) has the following structure:
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With respect to claim 90, Han discloses L2 is absent. [Han, 0872]
With respect to claim 105, Han discloses a pharmaceutical composition comprising the compound and at least one pharmaceutically acceptable excipient. [Han, 0031]
Han further discloses the compound may be labeled with a radioisotope by any means known in the art. [Han, 0669] Han also discloses MC2R and other melanocortin receptors MC1R, MC3R, MC4R, and MC5R form a family of G protein coupled receptor that are selectively activated by different melanocortin peptides. [Han, 0004]
Han does not disclose the compound comprises Rb.
However, with respect to claim 79 and 91, Morse discloses a melanocortin subtype-1 receptor (MC1R) modulator that is labeled with a radioisotope using a chelating moiety:
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379
484
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[Morse, Page 6, Formula IA]
Wherein,
Rb is -L3-Q,
L3 is a linker, and
Q is a chelating moiety (i.e., DOTA, DTPA, DOTP, DOTMA, TETA, DOTAM, CB-TE2A, NOTA) or a radionuclide complex of the chelating moiety. [Morse, 0056-0061, 0064]
With respect to claim 93, 95, and 96, Morse discloses, in one embodiment, the linker (L) is C1-C20 alkylamide (e.g. acetamide, ethylacetamide, propylacetamide, etc.). [Morse, 0058]
So, Morse discloses L3 is -L6-L5-L7-L8-L9-L10-, wherein:
-L4- is C1-20 alkylene
-L5- is absent
-L7- is absent
-L8- is absent
-L9-L10 is -NHC(=O)-C1 alkylene.
In a specific embodiment, Morse discloses 225Ac-MC1RL-DOTA:
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438
534
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[Morse, Figure 1B]
Wherein,
Rb is -L3-Q,
L3 is a linker, and
Q is a chelating moiety, DOTA.
With respect to claim 93, Morse discloses the linker (L) of 225Ac-MC1RL-DOTA is aminohexanoic acid. [Morse, Figure 1B]
So, Morse discloses L3 is -L4-L7-L9-, wherein:
-L4- is -C(=O)-
-L7- is C5 alkylene
-L9- is -NH-.
In a specific embodiment, Morse discloses [Eu3+]-MC1RL-DOTA:
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305
514
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[Morse, Figure 19]
Wherein,
Rb is -L3-Q,
L3 is a linker, and
Q is a chelating moiety, DOTA.
With respect to claim 93 and 99, Morse discloses the linker is D-di-Glu. [Morse, Figure 19]
So, Morse discloses L3 is -L5-, wherein:
-L5- is 2 independent natural amino acids, D-Glu. [Morse, Figure 19]
Modifying the compound disclosed by Han by conjugating a chelating moiety (i.e., DOTA, DTPA, DOTP, DOTMA, DOTAM) thereto via a linker results in the compound of claim 79 and 91.
Modifying the compound disclosed by Han by conjugating a chelating moiety (DOTA) thereto via a D-di-Glu linker results in the compound of claim 79, 91, 93, and 99, wherein L5 is:
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Modifying the compound disclosed by Han by conjugating a chelating moiety (DOTA) thereto via an aminohexanoic acid linker results in the compound of claim 79, 91, and 93.
Modifying the compound disclosed by Han by conjugating a chelating moiety (i.e., DOTA, DTPA, DOTP, DOTMA, DOTAM) thereto via a C1-C20 alkylamide (e.g. acetamide, ethylacetamide, propylacetamide, etc.) linker, results in the compound of claim 79, 91, 93, 95, and 96.
It would be obvious to one of ordinary skill in the art to select the aforementioned MC2R modulator disclosed by Han as the lead compound. Han is directed to a genus of MC2R modulators. Han further discloses these modulators may be modified by isotopic labeling via means known in the art. Han also provides illustrative examples of these modulators, including the aforementioned MC2R modulator, which serve as representatives members of the genus. Accordingly, a POSITA would have recognized the exemplified modulators as suitable for such modification would have been motivated to modify the aforementioned MC2R modulator, in view of Han’s teachings.
It would be obvious to one of ordinary skill in the art to modify the compound disclosed by Han by conjugating a chelating moiety thereto via a linker and have a reasonable expectation of success.
Han discloses a melanocortin receptor (MC2R) modulator that may be labeled with a radioisotope via means known in the art. Han further discloses MC2R and other melanocortin receptors, including MC1R, form a family of G protein coupled receptors that are selectively activated by different melanocortin peptides. Morse discloses a melanocortin receptor (MC1R) targeting compound that is suitable for radiolabeling by conjugating a chelating moiety (i.e., DOTA, DTPA, DOTP, DOTMA, DOTAM) to the modulator via a linker. In a specific embodiment, Morse discloses a MC1R targeting compound that is conjugated to DOTA via a D-di-Glu, an aminohexanoic acid, or alkylamide linker. Thus, Morse demonstrates that a melanocortin receptor modulator may be radiolabeled by conjugating a chelating moiety thereto via a linker. Accordingly, the combined teachings of Han and Morse suggest that the MC2R modulator disclosed by Han may be radiolabeled by conjugating a chelating moiety (i.e., DOTA) to the modulator via a linker (i.e., D-di-Glu, aminohexanoic acid, alkylamide). Therefore, it is reasonable to expect the compound disclosed by Han may be modified by conjugating a chelating moiety thereto via a linker. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) Morse discloses that conjugating a melanocortin receptor modulator to a chelating moiety via a linker enables chelation with an alpha-particle or beta-particle emitter radionuclide and enables the delivery of ionizing radiation to a target tissue. [Morse, 0064, 0068] Therefore, one would have been motivated by the expectation that the aforementioned modification could enable the MC2R modulator disclosed by Han to be chelated with an alpha-particle or beta-particle emitter radionuclide and delivered to a target tissue.
Claims 79-84, 87, 90- 93, 100-102, and 105 are rejected under 35 U.S.C. 103 as being unpatentable over Han, in view of Miao (US 2015/0239952 A1, Published 8/27/2015).
With respect to claim 79, Han discloses the following compound of Formula (I), a melanocortin subtype-2 receptor (MC2R) modulator.
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[Han, 0872]
wherein:
R1 is Ra
Ra is -CH2NR8-L2-Rb
L2 is absent
Y is N,
L1 is -C(=O)-
R2 is a C6-heterocylcoalkyl
R2 is substituted with R3a and R3b
R3a is C1-fluroalkyl
R3b is -OR9
R9 is C2 alkyl
R6 is C2 alkyl
R7 is C2 alkyl
X1 is N
X2 is N
n is 0
m is 1
R4 is hydrogen. [Han, 0872]
With respect to claim 80, Hand discloses R2 is:
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173
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. [Han, 0872]
With respect to claim 81, Han discloses R3a is -CF3, R3b is -OCH2CH3, and R3c is hydrogen. [Han, 0872]
With respect to claim 82, Han discloses R6 is -CH2CH3 and R7 is -CH2CH3. [Han, 0872]
With respect to claim 83, Han discloses the compound has the structure of Formula (VI), wherein X3 is N. [Han, 0872]
With respect to claim 84, Han discloses the compound has the structure of Formula (VIb).
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With respect to claim 87, Han discloses R3a is -CF3, R3b is -OCH2CH3, R3c is hydrogen, and R4 is hydrogen. [Han, 0872]
With respect to claim 88, Han discloses the compound of Formula (I) has the following structure:
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With respect to claim 90, Han discloses L2 is absent. [Han, 0872]
With respect to claim 105, Han discloses a pharmaceutical composition comprising the compound and at least one pharmaceutically acceptable excipient. [Han, 0031]
Han further discloses the compound may be labeled with a radioisotope by any means known in the art. [Han, 0669] Han also discloses MC2R and other melanocortin receptors MC1R, MC3R, MC4R, and MC5R form a family of G protein coupled receptor that are selectively activated by different melanocortin peptides. [Han, 0004]
Han does not disclose the compound comprises Rb.
With respect to claim 79, Miao discloses a melanocortin subtype-1 receptor (MC1R) targeting compound that may be labeled with a radioisotope using a chelating moiety:
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Wherein,
Rb (denoted as “Y1-X”) is -L3-Q,
L3 (denoted as “X”) is a linker, and
Q is a chelating moiety (denoted as “Y1”). [Miao, 0039, 0019]
With respect to claim 91 and 92, Morse discloses the chelating moiety is DOTA, DTPA
DO3A, or DO2A. [Miao, 0039, 0019]
In a more specific embodiment, Miao discloses a melanocortin subtype-1 receptor (MC1R) targeting compound that is labeled with a radioisotope using a chelating moiety:
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[Miao, 0079]
Wherein,
Rb is -L3-Q,
L3 is a linker, norleucine (Nle), and
Q is a chelating moiety, DOTA. [Miao, 0079, Page 18 – Table 1A]
With respect to claim 93, Miao discloses the linker is Nle. [Miao, 0079, Page 18, Table 1A]
So, Miao discloses L3 is -L5-, wherein:
-L5- is an unnatural amino acid.
With respect to claim 100, 101, and 102, Miao discloses the linker, Nle, may be acylated preferably with a C(=O)C1-10 alkyl group. Miao discloses the acyl group at the terminal amine position, results in an amide linkage, which, after administration, may be cleaved. [Miao, 0019, 0048, 0049]
Modifying the compound disclosed by Han by conjugating a chelating moiety (i.e., DOTA,
DO3A, DO2A) thereto via a linker results in the compound of claim 79 and 91.
Modifying the compound disclosed by Han by conjugating DO3A thereto via a linker results in the compound of claim 79 and 92.
Modifying the compound disclosed by Han by conjugating a chelating moiety (DOTA, DO3A, DO2A) thereto via a norleucine linker results in the compound of claim 79 and 93.
Modifying the compound disclosed by Han by conjugating DOTA thereto via an acetyl-norleucine linker results in the compound of claim 79 and 102, wherein the compound of Formula (I) is:
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Modifying the compound disclosed by Han by conjugating DO3A thereto via an acetyl-norleucine linker results in the compound of claim 93, 100, and 101, wherein:
L3 is:
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; and
Q is:
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It would be obvious to one of ordinary skill in the art to select the aforementioned MC2R modulator disclosed by Han as the lead compound. Han is directed to a genus of MC2R modulators. Han further discloses these modulators may be modified by isotopic labeling via means known in the art. Han also provides illustrative examples of these modulators, including the aforementioned MC2R modulator, which serve as representatives members of the genus. Accordingly, a POSITA would have recognized the exemplified modulators as suitable for such modification been motivated to modify the aforementioned MC2R modulator, in view of Han’s teachings.
It would be obvious to one of ordinary skill in the art to modify the compound disclosed by Han by conjugating a chelating moiety thereto via a linker and have a reasonable expectation of success.
Han discloses a melanocortin receptor (MC2R) targeting compound that may be labeled with a radioisotope via means known in the art. Han further discloses MC2R and other melanocortin receptors, including MC1R, form a family of G protein coupled receptors that are selectively activated by different melanocortin peptides. Miao discloses a melanocortin receptor (MC1R) targeting compound that is suitable for radiolabeling by conjugating a chelating moiety (i.e., DOTA, DO3A, DO2A) to the targeting compound via a linker. In a specific embodiment, Miao discloses the MC1R targeting compound is conjugated to DOTA via a norleucine linker or an acetylated norleucine linker, such as acetyl-norleucine. Thus, Miao demonstrates that a melanocortin receptor targeting compound may be radiolabeled by conjugating a chelating moiety thereto via a norleucine or acetyl-norleucine linker. Accordingly, the combined teachings of Han and Miao suggest that the MC2R targeting compound disclosed by Han may be radiolabeled by conjugating a chelating moiety (i.e., DOTA, DO3A, DO2a) to the targeting compound via a linker (i.e., norleucine or acetyl-norleucine). Therefore, it is reasonable to expect the compound disclosed by Han may be modified by conjugating a chelating moiety thereto via a linker. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) Miao discloses that conjugating a melanocortin receptor targeting compound to a chelating moiety via a linker enables chelation with an appropriate radioisotope and may be employed in targeted radiation. [Miao, 0029] Therefore, one would have been motivated by the expectation that the aforementioned modification could enable the MC2R targeting compound disclosed by Han to be chelated with an appropriate radioisotope and employed in targeted radiation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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