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 .
Status of the Claims
Claims 1-50 are pending in the instant application and subject to examination herein.
Claim Objections
Claim 25 is objected to because of the following informalities: The two palladium catalysts “Pd2dba3 (dibenzylidene acetone)” and “Pd(PPh3)4” are not separated by a comma and therefore appear as if they are intended to represent a singular palladium catalyst species. 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 27-28, 31-36, 48 and 50 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 27 is drawn to a process for preparing a scalemic or racemic mixture of Galbulimima alkaloid GB18, comprising a mixture of enantiomers of provided Formulae (1) and (2), the process comprising using at least one compound from a provided Markush group. The claim is indefinite because the claim does not provide any definite step to be performed. The requirement of “using” a compound of the provided Markush group is indefinite because the claim does not define how any of the disclosed compounds are to be used, whether as reactant(s), reagent(s), catalyst(s), analytical standard(s), or other use(s). Claim 28 depends from and further limits claim 27 by including a step to be performed that is a step of separating the scalemic or racemic mixture of GB18 into its separate enantiomers. While 28 does not have the condition of not having any step(s) to be performed, claim 28 does not resolve the indefiniteness introduced in claim 27, because the method remains a “process of preparing a scalemic or racemic mixture” of GB18, which requires at least one step to be performed that leads to the formation of a scalemic or racemic mixture of GB18, whereas the step to be performed in claim 28 does not result in a scalemic or racemic mixture of GB18 but rather eliminates the mixture by separating its components into the separate enantiomers.
Claim 31 is drawn to a method of antagonizing an opioid receptor in a subject in need of such antagonization, comprising administering to such1 subject a therapeutically effective amount of a compound of Formula (I). The use of the indefinite adjective “such” along with “subject” renders the claims as identifying a patient population that includes, but is not limited to, a subject who is in need of opioid receptor antagonization. The word “such” as an adjective, is defined to mean “of the same class, type or sort”2 which could include a subject who is in need of opioid receptor antagonization or a subject similar to, but not the same as, one who is who is in need of opioid receptor antagonization. The term “such subject” is included in the instant disclosure once, on page 8, in the same context as in claim 31, namely in the context of a method of antagonizing an opioid receptor. The instant disclosure does not anywhere provide background on the patient population that is in need of opioid receptor antagonization, nor any further patient population that is similar to, but distinct from the patient population that is in need of opioid receptor antagonization and thus could be identified not as “the” patient in need of opioid receptor antagonization but rather “such subject”. Claim 31 is indefinite because a person of ordinary skill in the art would not know the metes and bounds of claim 31 in regard to the indefinite patient population. Claims 32-36 depend from claim 31 and do not resolve the indefiniteness of the patient population subject to the method.
Claim 48 recites the limitation "a compound of formula I" in its preamble: “A compound of formula I, have the structure of any of one of the group consisting of. . .”. There is insufficient antecedent basis for this limitation in the claim. No “formula I” is provided in claim 48, and claim 48 is not dependent from any other claim that would provide an antecedent basis for “a compound of formula I”. Claim 49 depends from and further limits claim 48 but does not resolve the indefiniteness of the undefined “formula I” presented in claim 48.
Claim 50 is drawn to “Any process, method or compound as disclosed herein” and is indefinite because a person of ordinary skill in the art would not be able to discern what category of invention is being claimed, since the claim is simultaneously drawn to multiple categories of invention (i.e., process/method and composition of matter).
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.
Claims 43 and 47 are 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 43 depends alternately from claims 41 or 42, and further limits the genus of compounds under Formula (II), which is introduced in claim 41 and further limited in claim 42, and shown below, bearing substituents R1-R2 and R4-R5, variables X, Y and Z, and with further limitations described in each of claims 41 and 42:
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In parent claim 41, substituent R1 may be any of deuterium, halogen, hydroxy, CO2H, C1-C6-alkoxy, C1-C6-alkyl, C6-C10-aryl, C3-C7-heterocyclyl, or C5-C14-heteroaryl, with the aryl, heterocyclyl or heteroaryl being optionally further substituted. Claim 42 further limits the genus of Formula (II), including limiting the scope of substituent R1 to wherein R1 is C6-C10-aryl or C5-C10-heteroaryl. Claim 43 further limits the genus of Formula (II) to wherein the compound is a compound of sub-Formula (1), shown below:
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As shown in the figure above, sub-Formula (1) has a 6-methylpiperidin-2-yl group as R1, which is a C6-heterocyclyl group, and therefore does not fall within the limitations of claim 42. Thus, claim 43 depends (alternately) from claim 42 but does not include all the limitations of claim 42.
Claim 47 depends alternately from claims 45 or 46, and further limits the genus of compounds under Formula (II), which is introduced in claim 45 and further limited in claim 42, and shown below, bearing substituents R1-R2 and R4-R5, variables X, Y and Z, and with further limitations described in each of claims 41 and 42:
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In parent claim 45, substituent R1 may be any of deuterium, halogen, hydroxy, CO2H, C1-C6-alkoxy, C1-C6-alkyl, C6-C10-aryl, C3-C7-heterocyclyl, or C5-C14-heteroaryl, with the aryl, heterocyclyl or heteroaryl being optionally further substituted. Claim 46 further limits the genus of Formula (II), including limiting the scope of substituent R1 to wherein R1 is C6-C10-aryl or C5-C10-heteroaryl. Claim 47 further limits the genus of Formula (II) to wherein the compound is a compound of sub-Formula (1), shown below:
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As shown in the figure above, sub-Formula (1) has a 6-methylpiperidin-2-yl group as R1, which is a C6-heterocyclyl group, and therefore does not fall within the limitations of claim 46. Thus, claim 47 depends (alternately) from claim 46 but does not include all the limitations of claim 46.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
Claims Free of the Prior Art
Claims 1-26, 29-30, 37-42, 45-46 and 49 are allowed. The following is a statement of reasons for the indication of allowable subject matter: Prior art does not teach or reasonably suggest, alone or in combination, a process for preparing a scalemic or racemic mixture of Galbulimima alkaloid GB18, comprising a mixture of the enantiomers of Formula (1) and (2), comprising the sequential steps disclosed in claim 1 and/or the additional limitations of claims 2-26. Prior art does not teach or reasonably suggest, alone or in combination, any of the specific compounds disclosed in claims 29-30. Prior art does not teach or reasonably suggest, alone or in combination a method of treating a disorder selected from the Markush group of disorders disclosed in claim 37, comprising administering to the subject in need thereof a compound of Formula (I), disclosed therein. Prior art does not teach or reasonably suggest, alone or in combination a method of antagonizing an opioid receptor in a subject in need of such agonization, comprising administering to the subject a therapeutically effective amount of a compound of Formula (II) disclosed in claim 41. Prior art does not teach or reasonably suggest, alone or in combination a method of treating pain, itching, depression or dissociative hallucination in a subject in need of such treatment, comprising administering to the subject a therapeutically effective amount of a compound of Formula (II) disclosed in claim 45.
Closest Prior Art:
The closest prior art is found in Rinner (Rinner, U.; Chapter 2: Galbulimima Alkaloids; Ed: Knolker, H.-J.; The Alkaloids: Chemistry and Biology, v78, pp109-166; Academic Press, 2017). Rinner provides a comprehensive review of the isolation, structural features, biological properties and known synthetic routes toward Galbulimima alkaloids (Abstract, page 109). Rinner discloses the structure of GB18 within the subgroup of Class 1 Galbulimima alkaloids (Figure 1, page 112). Rinner discloses that Galbulimima alkaloids are isolated from the bark of Galbulimima belgraveana, a bark known to be used by the native people in Papua New Guinea, Indonesia, and Northern Australia, who have taken advantage of the hallucinogenic properties of the bark in the treatment of abdominal pain and, by consuming, to reach a state of trance (page 113). While Rinner thus discloses that GB18, as a component of G. belgraveana bark, has been administered in a method to treat pain, a person of ordinary skill in the art, at the effective time of filing would not have a reasonable expectation of success in a method of treating pain comprising administering the enantiomer of GB18 to a subject in need of pain treatment, and the instant claims that regard methods that comprise pain treatment are all directed at genera of compounds based on a scaffold of the non-natural enantiomer of GB18, for which no prior art is found, either in Rinner or elsewhere. Rinner further does not disclose any de novo synthesis of GB18 itself or any other compound claimed among the instant claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Italics used for emphasis by Examiner.
2 See, for example, Merriam-Webster dictionary: https://www.merriam-webster.com/dictionary/such
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