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 .
Current Status
This action is responsive to the amended claims of 09/01/2023. Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are pending and have been examined on the merits.
Note, no restriction/election requirement has been made of record.
Priority
The effective filing date is 03/02/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/01/2023 and 08/05/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are objected to because of the following informalities. Appropriate correction is required.
In claims 1 and 25, please strike the comma after “amide” and before “(Compound A)” in line 4 of claim 1 and line 5 of claim 25. The comma is unnecessary and separates the chemical name from the related compound name (i.e., Compound A). Dependent claims 2-5, 7, 9-10, 12, 26, 28, 30-35, and 40 are similarly objected since they do not rectify the issue.
In claims 1 and 25, the annotated bond in the structure of compound A does not properly link the N and O atoms
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. Please provide a structure where the bond is clearer and connects the two atoms. The claim and overall structure for compound A is not indefinite because the claim also recites the chemical name. Dependent claims 2-5, 7, 9-10, 12, 26, 28, 30-35, and 40 are similarly objected since they do not rectify the issue.
Claim 25 recites “an individual” in line 2 and “a patient” in the last line. For consistency, please replace “an individual” in line 2 with “a patient”. This is consistent with the terminology used in the dependent claims, e.g., claim 33. Dependent claims 26, 28, 30-35, and 40 are similarly objected since they do not rectify the issue.
Claim 25 recites “having an AAPS of six” in line 2. Please replace with “having a baseline AAPS of six” for consistency with the terminology used in the dependent claims, e.g., claim 33. Dependent claims 26, 28, 30-35, and 40 are similarly objected since they do not rectify the issue.
Claim 30 has a strike through the word “method” in line 1 and so reads “The of claim 25”. Please un-strike the word “method”.
Claim Interpretation
Claims 25-26, 28, 30-35, and 40 recite an average abdominal pain score (AAPS). This scale is understood based on the disclosure at Pg. 11 final paragraph of the specification: “treatment of pain is assessed on the Average Abdominal Pain Score (AAPS). The Abdominal Pain Score (APS) is a single-question, 11-point numeric rating scale in which 0 represents no abdominal pain and 10 represents the worst possible abdominal pain.”
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.
Claims 25-26, 28, 30-31, and 33-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by LASSEN (WO 2018/208848).
Regarding claims 25 and 33-34, LASSEN teaches a method for treating or alleviating abdominal pain comprising administering to a patient a therapeutically effective amount of compound A
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(i.e., the instant compound A) or a pharmaceutically acceptable salt or crystal thereof (Pg. 140 claim 1 & Pg. 152 claim 9-10). LASSEN further teaches administration of the compound A to patients with abdominal pain due to Crohn’s disease with an average abdominal pain scope (AAPS) of ≥4 (i.e., baseline AAPS) (Pg. 138 ¶157-159). The AAPS is an 11-point scale from 0 (no pain) to 10 (worst pain) (Pg. 138 ¶159).
Examiner understands the reference AAPS of ≥4 to anticipate the instant AAPS of ≥6 in view of MPEP 2131.02(III). Similar to In re Petering wherein a small genus defining ~20 compounds was found to anticipate a single species, the prior art genus of AAPS ≥4 is understood to be a very small genus (i.e., 7 individual scores of 4-10). The prior art AAPS of ≥4 substantially overlaps with the instant ≥6, ≥6.5, and ≥7. Since the prior art range is so small (i.e., 7 scores), the artisan would be able to at once envisage all embodiments of the reference AAPS. Moreover, since the artisan would at once envisage the instant ranges from the prior art range, Examiner concludes the prior art range discloses the claimed ranges with sufficient specificity to anticipate the claims (see MPEP 2131.03(II)).
Regarding claims 26, 28, 30, and 35, LASSEN teaches compound A is administered in a dose from 10-500 mg (Pg. 153 claim 17), or a dose of 25 or 50 or 100 mg (Pg. 153 claim 19), or a dose of 75 mg (Pg. 20 sect. 1.17). LASSEN further teaches the dosages are given once, twice, or three times per day (Pg. 153 claim 20).
Regarding claim 31, LASSEN teaches the compound A is administered in an anhydrous, non-solvated crystalline form (Pg. 153 claim 21).
Claims 25-26, 28, 30, 32 and 33-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YACYSHYN (Yacyshyn B.R. et al., Crohn’s & Colitis, pub. 23 Oct. 2020, 3(1), 1-11, cited in IDS of 09/01/2023).
Note: YACYSHYN is published within the 1-year grace period and shares some authors with the instant inventors, thus, it may be eligible for a 102(b)(1) exception. Please see MPEP 2153.01(a): “the applicant may establish that the AIA 35 U.S.C. 102(b)(1)(A) exception applies by way of an affidavit or declaration under 37 CFR 1.130(a). MPEP § 2155.01 discusses the use of affidavits or declarations to show that a disclosure was an inventor-originated disclosure made during the grace period.”
Regarding claims 25 and 33-34, YACYSHYN teaches patients with Crohn’s disease experiencing abdominal pain were treated with orlorinab (which is understood to be another name for the instant compound A) (Pg. 1 Background). The patient has an average abdominal pain score (AAPS) of ≥4 (Pg. 3 Subjects) wherein the AAPS is an 11-point numeric rating scale from 0 (no pain) to 10 (worst pain) (Pg. 3 Right Col. ¶2). Using the same logic applied to instant claims 25 and 33-34 above, based on MPEP 2131.02(III) and 2131.03(II), the prior art range of AAPS ≥4 (i.e., 4-10) discloses the claimed ranges with sufficient specificity to anticipate the claims.
Regarding claims 26, 28, 30, and 35, YACYSHYN teaches doses of 25 and 100 mg were given three times a day (Pg. 1 Methods & Pg. 7 Fig. 2).
Regarding claim 32, YACYSHYN teaches the 25 and 100 mg TID doses resulted in ≥30% improvement from baseline AAPS in a majority of patients (Pg. 7 Fig. 2).
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 1-5, 7, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over LASSEN (WO 2018/208848) and IWATA (Iwata, Y. et al., Bioorganic & Medicinal Chemistry Letters, 2015, 25, 236-240).
Determining the Scope and Contents of the Prior Art:
LASSEN teaches a method for treating or alleviating visceral pain comprising administering to a patient a therapeutically effective amount of compound A (i.e., the instant compound A) or a pharmaceutically acceptable salt or crystal thereof (Pg. 140 claim 1 & Pg. 152 claim 9); wherein the visceral pain is abdominal pain (Pg. 152 claim 10). LASSEN teaches compound A is administered in a dose from 10-500 mg (Pg. 153 claim 17), or a dose of 25 or 50 or 100 mg (Pg. 153 claim 19), or a dose of 75 mg (Pg. 20 sect. 1.17). LASSEN further teaches the dosages are given once, twice, or three times per day (Pg. 153 claim 20). LASSEN teaches the compound A is administered in an anhydrous, non-solvated crystalline form (Pg. 153 claim 21). Further, LASSEN teaches selective activation of CB2 receptors in the patient experiencing visceral pain by administration of compound A (Pg. 4 ¶16); compound A was shown to be a full agonist of the CB2 receptor (Pg. 110 ¶60).
IWATA teaches CB2 agonists exhibit an analgesic effect in a visceral hypersensitivity model which is a well-known animal model of IBS, thus, selective CB2 agonists are of particular interest as an emerging therapy for IBS (Pg. 236 Left Col. ¶3). IWATA teaches IBS is a gastrointestinal disorder characterized by abdominal pain and is classified into three categories based on bowel habits and stool forms: IBS-D, IBS-C, and IBS-Mixed (Pg. 236 Left Col. ¶2). IWATA further teaches administration of a CB2 agonist to the visceral hypersensitivity model rat improved the subject’s pain threshold (Pg. 239 Figure 2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
LASSEN does not teach the abdominal pain is due to IBS.
IWATA does not teach administration of the instant compound A.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of abdominal pain and possesses the technical knowledge necessary to make adjustments to the target patient population to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding the role of CB2 agonists in treatment of IBS-related pain and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references LASSEN and IWATA.
Regarding claims 1-4, the artisan would find it obvious to treat abdominal pain due to IBS by administering the instant compound A to a patient. The artisan would be motivated to do so, since:
1) LASSEN teaches treatment of visceral abdominal pain by administering compound A (Pg. 152 claim 9-10) wherein compound A is a selective CB2 agonist (Pg. 4 ¶16 & Pg. 110 ¶60); and
2) IWATA teaches the analgesic effect of selective CB2 agonists in a visceral pain model of IBS (Pg. 236 Left Col. ¶3) wherein treatment with a CB2 agonist improved pain threshold (Pg. 239 Fig. 2).
The artisan would recognize LASSEN and IWATA as related references regarding treatment of visceral abdominal pain by administration of selective CB2 agonists. Thus, the artisan would be motivated to apply LASSEN’s method of treatment (i.e., administering compound A) to a patient with abdominal pain due by IBS, to take advantage of the known analgesic effect of CB2 agonists in IBS, as recognized by IWATA. Further, since IWATA teaches IBS is characterized by abdominal pain and comprises three species including IBS-C and IBS-D (Pg. 236 Left Col. ¶2), the artisan would recognize both patients with IBS-C and IBS-D as suffering from abdominal pain. In view of the teachings of both LASSEN and IWATA regarding the analgesic effect of CB2 agonists, the artisan would recognize both types of IBS as ripe for treatment with the selective CB2 agonist compound A.
Regarding claims 5, 7, 9-10, since the method of instant claim 1 is obvious (above), and since the teachings of LASSEN match exactly the instantly claimed dosage amounts (Pg. 153 claim 17 & 19; Pg. 20 sect. 1.17), dosage times (Pg. 153 claim 20), and crystalline form (Pg. 153 claim 21), the artisan would find the instant claims obvious.
Claims 1 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over LASSEN (WO 2018/208848) and IWATA (Iwata, Y. et al., Bioorganic & Medicinal Chemistry Letters, 2015, 25, 236-240) as applied to claim 1 above, further in view of ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53) and YACYSHYN (Yacyshyn B.R. et al., Crohn’s & Colitis, pub. 23 Oct. 2020, 3(1), 1-11, cited in IDS of 09/01/2023).
Determining the Scope and Contents of the Prior Art:
LASSEN and IWATA teach instant claim 1 (see ¶21 above). LASSEN further teaches administration of the compound A in subjects experiencing abdominal pain wherein their pain level before and after treatment is defined by a weekly average abdominal pain scope (AAPS) (Pg. 138 ¶157-159). IWATA teaches about 30% improvement in pain threshold after administration of a CB2 agonist (Pg. 239 Fig. 2).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. ¶2) and the effective dose may be different for different patients (Pg. 48 Left Col. ¶4). ANSEL further teaches the schedule of dosage or the dosage regimen is determined based on a drug’s duration of action, pharmacokinetics, and characteristics of the dosage form (Pg. 40 Right Col. ¶2).
YACYSHYN teaches olorinab (which is understood to be another name for the instant compound A) was administered to patients with chronic abdominal pain associated with Crohn’s disease and resulted in ≥30% reduction from baseline in weekly average abdominal pain score (AAPS) (Pg. 7 Fig. 2-Pg. 8 Fig. 3). Baseline AAPS is understood to be measured before treatment began (Pg. 6 Right Col. ¶1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
LASSEN and IWATA do not teach ≥30% improvement in AAPS.
ANSEL does not teach the instant method of treatment.
YACYSHYN does not teach treatment of IBS.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for improving the baseline AAPS in IBS patients and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcome. Said artisan has also reviewed the problems in the art regarding the role of CB2 agonists in treatment of IBS-related pain and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references LASSEN, IWATA, ANSEL, and YACYSHYN.
Further in view of ANSEL, the artisan would have been motivated to optimize the dosage of compound A and would expect optimization of the resulting treatment outcome (i.e., improvement in AAPS).
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").”
Furthermore, MPEP 2144.05(I) provides guidance about overlapping ranges: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists…Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
In the instant case, IWATA teaches about 30% improvement in pain threshold and LASSEN teaches use of the AAPS to track the pain level in patients with abdominal pain (Pg. 138 ¶157-159). Further, LASSEN teaches dosages of the compound A (see ¶21 above). These dosages exactly match the instantly claimed dosages (see claims 5, 7, & 9). Since ANSEL teaches the dosage regimen is based on duration of action, pharmacokinetics, and the dosage form (Pg. 40 Right Col. ¶2) and the effective dosing may be different for different patients (Pg. 48 Left Col. ¶4), the artisan would recognize the dosage amount and timings of compound A as a result-effective variable, i.e., a variable that achieves a recognized result – in this case, the % improvement in AAPS. Thus, the dosage and resulting % improvement in AAPS is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Therefore, the determination of the optimum or workable dosage regimen of compound A which would achieve a ≥30% improvement in AAPS would have been well within the practice of the artisan. Since IWATA teaches ~30% improvement with another CB2 agonist the artisan would be motivated to match or exceed that % improvement (see MPEP above “the normal desire of scientists or artisans to improve upon what is already generally known provides the motivation”). Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed dosage regimen, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Moreover, MPEP 2112.02.I states: “Under the principles of inherency, if a prior art device (e.g., compound), in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device (e.g., compound). When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process.” Here, the instantly claimed dosages of compound A are exactly taught by LASSEN; thus, compound A in its normal and usual operation of treating abdominal pain would be expected to necessarily cause a ≥30% improvement in AAPS.
Further in view of YACYSHYN, the artisan would have a reasonable expectation of success in causing a ≥30% improvement in AAPS by administering compound A to a patient with IBS-related abdominal pain since YACYSHYN teaches ≥30% reduction in AAPS (i.e., improvement) by administering the instant compound to patient with abdominal pain. While the two patient populations do differ (i.e., IBS vs. Crohn’s), both diseases are recognized to cause abdominal pain by the above teachings and the analgesic effects of compound A/CB2 agonists for abdominal pain are known (see above 103).
Claims 25-26, 28, 30-31, and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over LASSEN (WO 2018/208848).
Determining the Scope and Contents of the Prior Art:
The teachings of LASSEN are above, ¶15.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
LASSEN does not explicitly state the AAPS is ≥6, ≥6.5, or ≥7.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for improving patient AAPS and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding AAPS and the role of compound A as an analgesic for abdominal pain and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the reference LASSEN.
Regarding claims 25 and 33-34, in view of the teachings of LASSEN, the artisan would be motivated to administer compound A to a patient having an AAPS of ≥6, ≥6.5, or ≥7 in order to reduce their pain level. The artisan would have a reasonable expectation of success since LASSEN teaches treating abdominal pain by administration of compound A (Pg. 152 claim 9-10) and an embodiment wherein the compound is given to abdominal pain patients with an AAPS of ≥4 (Pg. 138 ¶157-159). Since LASSEN’s AAPS scale is taught as 0-10 (Pg. 138 ¶159) and the instant scale is also 0-10, an AAPS ≥4 (i.e., 4-10) encompasses and has significant overlap with the instant ranges of ≥6, ≥6.5, and ≥7 (i.e., 6/6.5/7-10). Thus, the artisan would recognize LASSEN’s method of treatment as including patients with AAPS of ≥6, ≥6.5, and ≥7. Further, since 10 is the highest pain level (Pg. 138 ¶159), the artisan would recognize a need for alleviation of pain in patients with scores approaching 10, i.e., ≥6, ≥6.5, or ≥7.
Regarding claims 26, 28, 30, and 35, since LASSEN teaches the method of claim 25 and the instant dosages (Pg. 153 claim 17, Pg. 153 claim 19, Pg. 20 sect. 1.17) and timings thereof (Pg. 153 claim 20), the instant claims are obvious.
Regarding claim 31, since LASSEN teaches the method of claim 25 and the anhydrous, non-solvated crystalline form (Pg. 153 claim 21), the instant claim is obvious.
Claims 25, 32, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over LASSEN (WO 2018/208848) as applied to claim 25 above, further in view of IWATA (Iwata, Y. et al., Bioorganic & Medicinal Chemistry Letters, 2015, 25, 236-240), ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53) and YACYSHYN (Yacyshyn B.R. et al., Crohn’s & Colitis, pub. 23 Oct. 2020, 3(1), 1-11, cited in IDS of 09/01/2023).
Determining the Scope and Contents of the Prior Art:
LASSEN teaches the method of claim 25, see ¶23 above. LASSEN further teaches the subject’s AAPS is tracked over 4 to 8 weeks of administration of compound A (Pg. 138 ¶157-159). LASSEN also teaches selective activation of CB2 receptors in the patient experiencing abdominal pain by administration of compound A (Pg. 4 ¶16); compound A is a full agonist of the CB2 receptor (Pg. 110 ¶60).
IWATA teaches CB2 agonists exhibit an analgesic effect in a visceral hypersensitivity model which is a well-known animal model of abdominal pain (Pg. 236 Left Col. ¶3 & Pg. 236 Left Col. ¶2). IWATA further teaches administration of a CB2 agonist to the animal model improved the subject’s pain threshold by about 30% (Pg. 239 Figure 2).
The teachings of ANSEL and YACYSHYN in ¶22, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
LASSEN does not teach wherein the baseline AAPS improves by ≥30% nor wherein compound A is administered for 12 weeks and the improvement in AAPS is for at least 6 of the 12 weeks.
IWATA does not teach the instant compound.
ANSEL does not teach the instant method of treatment.
YACYSHYN does not teach treatment of IBS.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for improving patient AAPS and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding dosages for compound A and the role of CB2 as an analgesic for abdominal pain and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references LASSEN, IWATA, ANSEL, and YACYSHYN.
Further in view of IWATA and ANSEL, the artisan would find the teachings of IWATA to be relevant to LASSEN since IWATA also teaches administration of a CB2 agonist for treatment of abdominal pain. Further, in view of ANSEL, the artisan would have been motivated to optimize the dosage/dosage regimen of compound A and would expect optimization of the resulting treatment outcome (i.e., improvement in AAPS). See MPEP 2144.05(II)(A) and 2144.05(I) citations above, ¶22.
In the instant case, IWATA teaches about 30% improvement in pain threshold (Pg. 239 Figure 2) and LASSEN teaches use of the AAPS to track the pain level in abdominal pain patients over an 8-week treatment course (Pg. 138 ¶157-159). The 30% improvement of IWATA approaches the instant ≥30% improvement in AAPS. The 8-week course of LASSEN approaches/is close to the instant 12-week course. Further, LASSEN teaches dosages of the compound A (see above 102) which exactly match the instantly claimed dosages (see claims 26, 28, 30, & 35). Since ANSEL teaches dosage regimens are based on duration of action, pharmacokinetics, and the dosage form (Pg. 40 Right Col. ¶2) and effective dosing may be different for different patients (Pg. 48 Left Col. ¶4), the artisan would recognize the dosage amount and regimen of compound A as a result-effective variable, i.e., a variable that achieves a recognized result – in this case, the % improvement in AAPS. Thus, the dosage regimen and resulting % improvement in AAPS is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Therefore, the determination of the optimum or workable dosage regimen (i.e., instant 12-week course) of compound A which would achieve a ≥30% improvement in AAPS sustained over at least 6 of the 12 weeks would have been well within the practice of the artisan. Since IWATA teaches ~30% improvement with another CB2 agonist the artisan would be motivated to match or exceed that % improvement (see MPEP above “the normal desire of scientists or artisans to improve upon what is already generally known provides the motivation”). Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed dosage regimen, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Moreover, regarding claim 32, MPEP 2112.02.I states: “Under the principles of inherency, if a prior art device (e.g., compound), in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device (e.g., compound). When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process.” Here, the instantly claimed dosages of compound A are exactly taught by LASSEN; thus, compound A in its normal and usual operation of treating abdominal pain would be expected to necessarily cause a ≥30% improvement in AAPS.
Further in view of YACYSHYN, the artisan would have a reasonable expectation of success in causing a ≥30% improvement in AAPS by administering compound A to a patient with abdominal pain since YACYSHYN teaches ≥30% reduction in AAPS (i.e., improvement) by administering the instant compound to patient with abdominal pain. Further, both YACYSHYN and LASSEN are drawn to treatment of pain in Crohn’s disease, providing even higher expectation of success.
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.
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Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 2,11-14, 24, 26, 28, and 30 of U.S. Patent No. 9,944,606 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims 2,11-14, 24, 26, 28, and 30 of US ‘606 are drawn to a method of treating pain comprising administering the instant compound A, referred to as compound 699, and various salts/crystal forms thereof
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘606 does not teach the pain is abdominal/due to IBS, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘606, LASSEN, IWATA, and ANSEL.
US ‘606 teaches the same compound as LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘606 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘606 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 2 and 4 of U.S. Patent No. 8,778,950 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims 2 and 4 of US ‘950 are drawn to the instant compound A, referred to as compound 699, and a pharmaceutical composition thereof. Further, see MPEP 804(II)(B)(1): “when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.” The compound of ‘950 is useful for treatment of pain (Pg. 1 abstract).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘950 does not teach the pain is abdominal/due to IBS, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘950, LASSEN, IWATA, and ANSEL.
US ‘950 teaches the same compound as LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘950 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘950 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1 and 15-16 of U.S. Patent No. 9,597,340 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims 1 and 15-16 of US ‘340 are drawn to composition of the instant compound A, referred to as compound 699. Further, see MPEP 804(II)(B)(1): “when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.” The compound of ‘340 is useful for modulating the CB2 receptor (Pg. 1 abstract).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘340 does not teach the treating abdominal pain, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘340, LASSEN, IWATA, and ANSEL.
US ‘340 teaches the same compound as LASSEN and both teach the compound is a CB2 modulator. Thus, the artisan would recognize LASSEN and US ‘340 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘340 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 19 and 32 of U.S. Patent No. 9,458,136 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims 19 and 32 of US ‘136 are drawn to the anhydrous non-solvated crystal form of instant compound A and a method of treating pain comprising administering the crystal form.
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘136 does not teach the pain is abdominal/due to IBS, the AAPS, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘136, LASSEN, IWATA, and ANSEL.
US ‘136 teaches the same compound as LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘136 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘136 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,183,930 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims of US ‘930 are drawn to solvates of instant compound A (i.e., crystal forms) (ref. claims 1-5), compositions thereof (ref. claims 6-8), and a method of treating pain comprising administering the solvate/crystal forms (ref. claims 9-11).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘930 does not teach the pain is abdominal/due to IBS, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘930, LASSEN, IWATA, and ANSEL.
US ‘930 teaches a crystal form of the compound A of LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘930 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘930 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 12-15, and 18 of U.S. Patent No. 11,560,369 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims of US ‘369 are drawn to a solvate crystalline form of instant compound A (ref. claims 1 and 12), compositions thereof (ref. claims 13-15), and a method of treating pain comprising administering the crystalline form (ref. claim 18).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘369 does not teach the pain is abdominal/due to IBS, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘369, LASSEN, IWATA, and ANSEL.
US ‘369 teaches a crystal form of the compound A of LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘369 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘369 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 4, 6-7, 16, and 19-20 of U.S. Patent No. 9,492,447 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims of US ‘447 are drawn to a composition of the instant compound A, referred to as compound 699 (ref. claims 1, 4, & 6-7), and a method of treating pain comprising administering the compounds and salts thereof (ref. claims 16 & 19-20).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘447 does not teach the pain is abdominal/due to IBS, the AAPS, the anhydrous crystal form, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘447, LASSEN, IWATA, and ANSEL.
US ‘447 teaches a composition of the compound A of LASSEN and both teach the compound is useful for treating pain. Thus, the artisan would recognize LASSEN and US ‘447 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘447 in view of the prior art references render the instant claims obvious.
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-9, 12-13, and 16-18 of U.S. Patent No. 9,867,822 in view of the LASSEN, IWATA, and ANSEL references applied in the 102 & 103 rejections above.
Determining the Scope and Contents of the Prior Art:
The claims of US ‘822 are drawn to a composition of the instant compound A or the anhydrous crystalline form thereof (ref. claims 1-9 and 12-13) and a method of modulating CB2 receptor comprising administering the instant compound A or the anhydrous crystalline form thereof (ref. claims 16-18).
The teachings of LASSEN, IWATA, and ANSEL in the 102 & 103 rejections, above, are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘822 does not teach the pain is abdominal/due to IBS, the AAPS, the instant dosages, or the effectiveness thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating abdominal pain and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding the analgesic properties of compound A and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘822, LASSEN, IWATA, and ANSEL.
US ‘822 teaches the compound A of LASSEN and both teach the compound is useful as a CB2 modulator. Thus, the artisan would recognize LASSEN and US ‘822 as equivalent/related references. Applying the logic applied to the instant claims in the 103 rejections, above, the claims of US ‘822 in view of the prior art references render the instant claims obvious.
Conclusion
Claims 1-5, 7, 9-10, 12, 25-26, 28, 30-35, and 40 are rejected.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625