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 .
DETAILED ACTION
This Office Action is Responsive to the Response to Election/Restriction filed 09/15/2025.
The preliminary amendment filed 02/22/2023, cancelled claims 1-30 and added claims 31-52.
Claims 31-52 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant’s election without traverse of compound BC19333 as the compound of formula (I),
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, and nonalcoholic steatohepatitis (NASH) as the disease, in the reply filed on 09/15/2023, is acknowledged.
In the course of the search, a method of treating NASH by administering
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was found to be allowable. As such, the search has been broadened to include liver cancer as the disease.
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species, and need not be extended beyond a proper Markush grouping. See subsection III.C.2, below, for additional guidance. See MPEP 803.02 III. A.
Claims 32-35, 38, 41-48 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claims 31, 36-37, 39-40 and 49-51 are examined on the merits herein.
Claim Objections
Claim 49 is objected to because of the following informalities:
-The Markush language in claim 49 is improper; commas are missing between Markush members and the conjunction “and” or “or” is missing prior to the recitation of the final Markush member.
See MPEP 2173.05(h) for guidance on proper Markush language.
-In claim 49, many of the structures are blurry and illegible. These structures must be replaced with clear depictions of the structures.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31, 36-37, 39, and 50-51 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.
-In claim 31, in the definitions of R2, Ra1, Rb1, Rc1, and Rd1, these groups are defined as “H, C1-6alkyl. . .each of which is optionally substituted with 1, 2. . .substituent independently selected from” another R group, which renders the claim indefinite because it is not clear how hydrogen can be substituted.
-In claim 37, in the definitions of Ra1, Rb1, Rc1, and Rd1, these groups are defined as “H, C1-6alkyl. . .each of which is optionally substituted with 1, 2. . .substituents independently selected from Rg,” which renders the claim indefinite because it is not clear how hydrogen can be substituted.
This rejection can be overcome by reciting, for example in the definition of R1, “wherein C1-6 alky. C1-6 haloalkyl, C2-4 alkenyl, and C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from R9.”
-Claim 49 is indefinite because on pages 39, 55, 79, 81, and 88 of the claim set, compound identifiers/names are recited, such as “BC19655,” without depicting the corresponding structure. Since other Markush members recite compound identifiers/names accompanied with a structural depiction, it is not clear if the missing structures are deleted members of the Markush group, or if the missing structures are inadvertently deleted from the Markush group.
In view of compact prosecution, for the purpose of applying prior art, these missing compounds are interpreted as deleted members of the Markush group.
-Claim 50 recites the limitation "said method is a method for treating a disease or condition" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim since claim 31 does not recite treating a disease or condition, but merely recites “A method of inhibiting CB-1 activity within a mammal.”
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 36 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 36 depends from claim 31, wherein claim 31 recites the following proviso:
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.
However, the first two compound depicted in claim 36 do not depict a compound wherein X2 or X3 is C(=O). As such, claim 36 recites limitations that are outside the scope of claim 31, from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
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 31, 36-37, 39-40 and 50-51 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting CB-1 activity or liver cancer by administering a compound of Formula (I) wherein X1 is O; X2 is NH, X3 is C=O; R7 or R8 are formula (I); R5 and R6 are H; R11 is C6 aryl, C6 cycloalkyl, C2-C3 alkyl, or C1-C2 alkyl substituted with C6 aryl; RN is H; or wherein RN and R11 forms a 5 or 6 membered heterocycloalkyl, does not reasonably provide enablement for a method of inhibiting CB-1 activity in a mammal, or a method of treating a disease or condition selected from obesity, fear, metabolic-related disorder, diabetes, dyslipidaemia, atherosclerosis, liver disorder, liver disease, nonalcoholic steatohepatitis, or cirrhosis by administering a compound of formula (I). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claim 31 is directed toward a method of treating CB-1 activity in a mammal by administering any compound of Formula (I):
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Claims 50 and 51 are also directed toward a method of treating the following diseases with compounds of Formula (I)--obesity, fear, metabolic-related disorder, diabetes, dyslipidaemia, atherosclerosis, liver disorder, liver disease, nonalcoholic steatohepatitis, cirrhosis, or liver cancer.
As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinical or an artisan with a PhD.
State of the Prior Art
WO 2011/137089 to Boxer (PTO-892) teaches a method of treating a disease responsive to activation of human PK-M2 comprising administering to a patient in need thereof, a therapeutically effective amount of a compound (pg. 71, claim 28). Boxer teaches the disease as cancer and specifically as liver cancer (pgs. 71-72, claims 29-32).
Boxer teaches the following as such compounds:
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(pgs. 66-67, claims 21),
wherein compounds 37-39 meet the limitations of instant Formula (I) when:
X1 is O
X2 is NR4, wherein R4 is H
X3 is C(O),
n is 0
R2, R3, R5, and R8 are H
R6 is the halo Cl or Br, or the C1 alkyl -CH3
R7 is S(O)2-N(RN)(R11), wherein RN is H and R11 is ring A, wherein ring A is C6 aryl substituted with two RA’s, wherein RA is C1 alkyl, -CH3.
Thus, while the prior art teaches compounds of Formula (I), such compounds are limited in scope and are taught as PK-M2 activators for the treatment of cancer.
The prior art is silent in reference to CB-1 inhibitory activity and compounds of Formula (I), and is silent in reference to treating diseases other than cancer with these compounds.
Predictability in the Art
Boxer shows that small changes in the core structure of compounds of Formula (I) or compounds structurally similar to compounds of Formula (I) produce changes in activity.
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AC50 values utilizing a pyruvate kinase for the following compounds are shown:
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([0165]);
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([0166]);
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([0167]). See also Table 4 in [0169].
As can be seen from the AC50 and MaxRes Values in the above tables, compounds with the same and similar core structures exhibit different activities.
As such, the activity of compounds of Formula (I) or those with the same core structure is unpredictable.
Working Examples
The instant specification only provides the efficacy, in terms of IC50 values, of the instant compounds as measured in a CB1 assay, for species of compounds of Formula (I) as depicted in instant claim 49.
Thus, the instant specification only provides in vitro working examples of the CB1 inhibitory activity of compounds of Formula (I), wherein X1 is O; X2 is NH, X3 is C=O; R7 or R8 are formula (I); R5 and R6 are H; R11 is C6 aryl, C6 cycloalkyl, C2-C3 alkyl, or C1-C2 alkyl substituted with C6 aryl; RN is H; or wherein RN and R11 forms a 5 or 6 membered heterocycloalkyl.
The instant specification provides zero working examples of administering the instantly claimed compounds to treat a disease or condition in a mammal.
Direction and Guidance
In view of the limited working examples of limited species of Formula (I), and the unpredictability in the activity of compounds of Formula (I), the instant specification lacks sufficient direction and guidance to use the invention as instantly claimed.
Quantity of Experimentation
The amount of experimentation required to determine which compounds of Formula (I) are effective to inhibit CB1, and effective to treat obesity, fear, metabolic-related disorders, diabetes, dyslipidaemia, atherosclerosis, liver disorder, liver disease, nonalcoholic steatohepatitis, cirrhosis, or liver cancer, would be astronomical. Such experimentation amounts to invention, not optimization; it is an undue amount of experimentation.
Thus, while being enabling for a method of inhibiting CB-1 activity by administering a compound of Formula (I) wherein X1 is O; X2 is NH, X3 is C=O; R7 or R8 are formula (I); R5 and R6 are H; R11 is C6 aryl, C6 cycloalkyl, C2-C3 alkyl, or C1-C2 alkyl substituted with C6 aryl; RN is H; or wherein RN and R11 forms a 5 or 6 membered heterocycloalkyl, the specification does not reasonably provide enablement for a method of inhibiting CB-1 activity in a mammal or a method of treating a disease or condition selected from obesity, fear, metabolic-related disorder, diabetes, dyslipidaemia, atherosclerosis, liver disorder, liver disease, nonalcoholic steatohepatitis, or cirrhosis by administering a compound of formula (I).
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 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 31, 36-37, 39-40, and 50-51 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2011/137089 to Boxer (published 2011, PTO-892).
Boxer teaches a method of treating a disease responsive to activation of human PK-M2 comprising administering to a patient in need thereof, a therapeutically effective amount of a compound (pg. 71, claim 28). Boxer teaches the disease as cancer and specifically as liver cancer (pgs. 71-72, claims 29-32).
Boxer teaches the following as such compounds:
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(pgs. 66-67, claims 21),
wherein compounds 37-39 meet the limitations of instant Formula (I) when:
X1 is O
X2 is NR4, wherein R4 is H
X3 is C(O),
n is 0
R2, R5, and R8 are H
R6 is the halo Cl or Br, or the C1 alkyl -CH3
R7 is S(O)2-N(RN)(R11), wherein RN is H and R11 is ring A, wherein ring A is C6 aryl substituted with two RA’s, wherein RA is C1 alkyl, -CH3.
"A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus." The species in that case will anticipate the genus. See MPEP 2131.02.
While Boxer does not explicitly teach “inhibiting CB-1 activity,” it is reasonable to assume that a method of administering a compound of instant Formula (I) would have the same properties since it is administered in the same dosage amount (Boxer teaches 0.001mg-300mg or 0.001mg/kg-300mg/kg ([0063]); and the instant specification teaches 0.1-1000mg or 0.01-200mg/kg (pg. 65)), to the same patient population (a mammal as recited in instant claim 31 and [0010] of Boxer), as that taught by the instant specification and claims. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties.
Thus, administering the instantly claimed compounds to the mammals of Boxer, in general, or to those mammal with liver cancer, would inhibit CB-1 activity. See also MPEP 2112.02.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
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 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 31, 36-37, 39-40 and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2011/137089 to Boxer (published 2011, PTO-892).
The teachings of Boxer in regard to claims 31, 36-37, 39-40, and 50-51 are applied as discussed above and incorporated herein.
Regarding claim 49, while Boxer teaches compounds of instant Formula (I), it differs from that of claim 49, in that it does not teach,
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, the elected species.
Boxer additionally teaches the following as a compound:
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.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to substitute the Me at the 4 position with a Cl, and the Me at the 3 position with a H in
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, to arrive at
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. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Boxer teaches its R2 and R3 as either H, halogen, or alkyl (pg. 64, claim 15), and specifically teaches R2 and R3 as H, Cl, or methyl (pg. 66, claim 19), and.
-Boxer exemplifies compounds with Cl and H at the R2/R3 position,
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, and teaches such a compound as therapeutically effective in terms of AC50 and MaxRes activity (pg. 53, Table 2).
As such, an ordinary skilled artisan would have been motivated to make such a substitution to predictably arrive at a compound with similar functionality, i.e., a compound effective to activate PK-M2 (pg. 70, claim 24).
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) (MPEP 2144.09(I)).” See also MPEP 2114.08
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622