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 .
Claim Objections
Applicant is advised that should claim 11 be found allowable, claim 26 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 26 is the same as claim 11 but adds the phrase “for use as a medicament” at the end of the claim. However, the pharmaceutical composition of claim 11 would be known to be a medicament as it is drawn to a “pharmaceutical composition” and would thus already be “used as a medicament”.
Claim 30 is objected to because of the following informalities: there should be a space between “claim18” to read as “claim 18”. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – 2nd paragraph
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 13, 14, 15, and 27 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.
Regarding claim 13, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Claim 14 recites the limitation "the combination or pharmaceutical composition for use according to claim 13" in the 1st line. There is insufficient antecedent basis for this limitation in the claim as claim 13, the claim from which it depends, is drawn to a combination and not to a pharmaceutical composition.
Claim 15 recites the limitation "the combination or pharmaceutical composition for use according to claim 13" in the 1st line. There is insufficient antecedent basis for this limitation in the claim as claim 13, the claim from which it depends, is drawn to a combination and not to a pharmaceutical composition.
Regarding claim 27, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Claim Rejections - 35 USC § 112 – 1st paragraph
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 13-15 and 27 are 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 combinations for treating hematopoietic disorders, does not reasonably provide enablement for combinations for prevention of the same. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Undue experimentation is a conclusion reached by weighing the noted factual considerations set forth below as seen in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). A conclusion of lack of enablement means that, based on the evidence regarding a fair evaluation of an appropriate combination of the factors below, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
These factors include:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on
the content of the disclosure.
The breadth of the claims/Nature of the Invention:
The claims are drawn to combinations for use in the prevention or treatment of a hematopoietic disorder . In the absence of an explicit definition in Applicant's specification, "Prevention" as recited in the instant claims, is interpreted to mean the complete and total blocking of all symptoms of a disorder for an indefinite period of time. Any therapy which merely reduces the number or severity of symptoms, or which is effective for a period shorter than the subject's remaining lifespan, is considered to be ineffective at preventing a disorder.
The state of the prior art:
Prevention of any disorder hematopoietic in the sense being used herein is not a recognized clinical outcome in the art.
The level of predictability in the art:
Regarding prevention, prevention of a disease is not the same as treatment of said disease. In order to prevent a disease, as opposed to merely delaying or reducing its symptoms, a dosing must either render the subject completely resistant to said disease after a single treatment or a limited number of treatments, or else, when continued indefinitely, continue to completely suppress the occurrence of said disease. In order to practice a preventative method, one of skill in the art must know the answer to several questions in addition to the effectiveness of the therapy in short-term relief of symptoms, including: 1) What is the duration of a single course of therapy? How often must the therapy be administered to completely suppress the disease? 2) Does the subject develop tolerance to the therapy over time? Does the disease eventually progress to a point where the therapy is unable to completely suppress all symptoms? For example, will a metastatic cancer eventually adapt to overcome treatments directed to preventing it from metastasizing into the bone? Or will a case of osteoporosis or rheumatoid arthritis ultimately progress to a point where symptoms develop regardless of which therapy is administered. 3) What are the long-term effects of the therapy? Does it cause progressive damage to the kidneys, liver, or other organs? Does the active agent accumulate in the subject's tissues? Is the minimum dose necessary to completely prevent the disease safe for long-term administration? Are there any steps that can be taken to reduce side effects? Additionally, because various physiological systems are interdependent and affect one another, any hypothetical preventative treatment would have to be broad-based and treat all of the various causes of a disorder. For example, because osteoporosis is, in the majority of cases, caused at least in part by a reduction in estrogen levels, a true preventative treatment for osteoporosis must be capable of preventing or reversing menopause in a subject. For this reason, many therapies which are suitable for short-term relief of symptoms are not suitable for lifelong prevention of disease. For example, antibiotics, chemotherapeutics, and antiviral drugs are not normally administered to healthy subjects in order to prevent the development of infection or cancer. Furthermore, a tissue can degenerate for a variety of reasons, including but not limited to, exposure to toxins, chronic viral infection, autoimmune attack, and deposition of amyloid protein. To be fully successful, a preventative method would have to guard against all of these possible insults.
The amount of direction provided by the inventor:
Applicant's specification discloses assays by which the inhibitory activity of various compounds can be determined. However, no guidance is given for determining which diseases can and cannot be prevented by the claimed method. No guidance is given in the specification suggesting any reason to believe that administration any of the claimed compounds can completely prevent all hematopoietic disorders.
The existence of working examples:
No working examples are given for the prevention of any disease. Note that lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the treatment of broad categories of disease with a single agent. See MPEP 2164.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
As mentioned above, the short-term usefulness of a therapy for relief of symptoms is no guarantee of its long-term usefulness for prevention of disease. Because no guidance is given for the use of the claimed therapeutic method for the long-term prevention of disease, one skilled in the art wishing to practice the invention would be unable to do so without first gathering information as to the long-term effectiveness of the therapy. In particular, one skilled in the art, in order to practice the invention for prevention of disease, would need to know whether the preventative effect remains potent over the long term. In order to answer these questions in the absence of any existing data, one skilled in the art, in order to practice the invention, would undertake long-term animal tests, preferably over a period of years, preferably involving a relatively long-lived experimental animal such as dogs or monkeys, or a human clinical trial. Animal experiments include, along with induction of the disease state, administration of the potential pharmaceutical compound and collection and analysis of data, additional burdens associated with compliance with animal welfare regulations, care, feeding, and other maintenance of the animals, dissection of dead animals to collect data, and disposal of dead animals after the protocol is finished. Administering the claimed compounds for a period of years to a suitable subject population is an undue amount of experimentation needed in order to practice the full range of the claimed invention. As prevention in the full sense is an extremely high bar for any clinical outcome, there is no reason to believe that the therapy would be successful, and any actual success would be a surprising and unpredictable result.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,473,295 in view of Pan et al. (Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia, Cancer Discovery, Volume 4(3), pp 362-375, March 2014).
The present claims are drawn to combinations of MLL inhibitors of formula I and a BCL-2 inhibitor; and optionally an additional antineoplastic agent. The MLL inhibitors are limited to those of compound A or salts thereof; the BCL-2 inhibitor is limited to various compounds such as venetoclax; and the additional antineoplastic agents are limited to azacitidine. The claims are also drawn to methods of treating hematopoietic disorders is one of various leukemias such as AML.
‘295 is drawn to MLL inhibitors having the same formula as compound A herein and methods of treating the same hematopoietic disorders such as AML with the same. What is not taught is the additional agents set forth in the present claims.
Pan teaches that selective inhibition by BCL-2 inhibitors such as ABT-199 are effective causing cell death in AML – see abstract, whole document. ABT-199 is known to be venetoclax.
As such, it would have been obvious to one of skill in the art at the time of the invention to add the additional BCL-2 inhibitors such as ABT-199 to the compositions and methods of ‘295 since both teach to treat the same diseases – AML. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). In the instant case, ‘295 teach that their compound A is effective in treating AML and Pan et al. teaches that venetoclax is effective in treating AML. Thus it would have been obvious to one of ordinary skill in the art at the time of the invention to combine the art recognized agents to form a new composition which will be used for the very same purpose with these references before them. One would have been motivated to combine these agents to form a new composition which would be used for the very same purpose. Likewise, while it would be obvious to add the “optionally, a therapeutically effective amount of at least one other antineoplastic agent” for the same reasons, it is noted that these additional agents are not required to be included by any of the present claims.
Claims 1-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/566,249 in view of Pan et al. . (Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia, Cancer Discovery, Volume 4(3), pp 362-375, March 2014).
The present claims are drawn to combinations of MLL inhibitors of formula I and a BCL-2 inhibitor; and optionally an additional antineoplastic agent. The MLL inhibitors are limited to those of compound A or salts thereof; the BCL-2 inhibitor is limited to various compounds such as venetoclax; and the additional antineoplastic agents are limited to azacitidine. The claims are also drawn to methods of treating hematopoietic disorders is one of various leukemias such as AML.
‘249 is drawn to MLL inhibitors having the same formula I herein and methods of treating the same cancers such as AML with the same. What is not taught is the additional agents set forth in the present claims.
Pan teaches that selective inhibition by BCL-2 inhibitors such as ABT-199 are effective causing cell death in AML – see abstract, whole document. ABT-199 is known to be venetoclax.
As such, it would have been obvious to one of skill in the art at the time of the invention to add the additional BCL-2 inhibitors such as ABT-199 to the compositions and methods of ‘249 since both teach to treat the same diseases – AML. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). In the instant case, ‘249 teach that their compound of formula I is effective in treating AML and Pan et al. teaches that venetoclax is effective in treating AML. Thus it would have been obvious to one of ordinary skill in the art at the time of the invention to combine the art recognized agents to form a new composition which will be used for the very same purpose with these references before them. One would have been motivated to combine these agents to form a new composition which would be used for the very same purpose. Likewise, while it would be obvious to add the “optionally, a therapeutically effective amount of at least one other antineoplastic agent” for the same reasons, it is noted that these additional agents are not required to be included by any of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-59 of copending Application No. 19/340,526 in view of Pan et al. . (Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia, Cancer Discovery, Volume 4(3), pp 362-375, March 2014).
The present claims are drawn to combinations of MLL inhibitors of formula I and a BCL-2 inhibitor; and optionally an additional antineoplastic agent. The MLL inhibitors are limited to those of compound A or salts thereof; the BCL-2 inhibitor is limited to various compounds such as venetoclax; and the additional antineoplastic agents are limited to azacitidine. The claims are also drawn to methods of treating hematopoietic disorders is one of various leukemias such as AML.
‘526 is drawn to MLL inhibitors having the same formula I herein and methods of treating the same cancers such as AML with the same. What is not taught is the additional agents set forth in the present claims.
Pan teaches that selective inhibition by BCL-2 inhibitors such as ABT-199 are effective causing cell death in AML – see abstract, whole document. ABT-199 is known to be venetoclax.
As such, it would have been obvious to one of skill in the art at the time of the invention to add the additional BCL-2 inhibitors such as ABT-199 to the compositions and methods of ‘526 since both teach to treat the same diseases – AML. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). In the instant case, ‘526 teach that their compound of formula I is effective in treating AML and Pan et al. teaches that venetoclax is effective in treating AML. Thus it would have been obvious to one of ordinary skill in the art at the time of the invention to combine the art recognized agents to form a new composition which will be used for the very same purpose with these references before them. One would have been motivated to combine these agents to form a new composition which would be used for the very same purpose. Likewise, while it would be obvious to add the “optionally, a therapeutically effective amount of at least one other antineoplastic agent” for the same reasons, it is noted that these additional agents are not required to be included by any of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of copending Application No. 18/560,233 in view of Pan et al. . (Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia, Cancer Discovery, Volume 4(3), pp 362-375, March 2014).
The present claims are drawn to combinations of MLL inhibitors of formula I and a BCL-2 inhibitor; and optionally an additional antineoplastic agent. The MLL inhibitors are limited to those of compound A or salts thereof; the BCL-2 inhibitor is limited to various compounds such as venetoclax; and the additional antineoplastic agents are limited to azacitidine. The claims are also drawn to methods of treating hematopoietic disorders is one of various leukemias such as AML.
‘233 is drawn to combinations of MLL inhibitors having the same formula I herein together with various additional agents and methods of treating the same cancers such as AML with the same. What is not taught is the BCL-2 inhibitors set forth in the present claims.
Pan teaches that selective inhibition by BCL-2 inhibitors such as ABT-199 are effective causing cell death in AML – see abstract, whole document. ABT-199 is known to be venetoclax.
As such, it would have been obvious to one of skill in the art at the time of the invention to add the additional BCL-2 inhibitors such as ABT-199 to the compositions and methods of ‘233 since both teach to treat the same diseases – AML. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). In the instant case, ‘233 teach that their compound of formula I is effective in treating AML and Pan et al. teaches that venetoclax is effective in treating AML. Thus it would have been obvious to one of ordinary skill in the art at the time of the invention to combine the art recognized agents to form a new composition which will be used for the very same purpose with these references before them. One would have been motivated to combine these agents to form a new composition which would be used for the very same purpose. Likewise, while it would be obvious to add the “optionally, a therapeutically effective amount of at least one other antineoplastic agent” for the same reasons, it is noted that these additional agents are not required to be included by any of the present claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2017/214367 which is drawn to combinations of agents where one is a MLL inhibitor having a different formula than claimed herein and indicates these MLL inhibitors can be optionally combined with BCL-2 inhibitors such as venetoclax (see page 61, lines 25-29).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRAVISS C MCINTOSH III whose telephone number is (571)272-0657. The examiner can normally be reached Monday-Friday 9AM-5:30PM EST.
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TRAVISS C. MCINTOSH III
Primary Examiner
Art Unit 1693
/TRAVISS C MCINTOSH III/Primary Examiner, Art Unit 1693