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 .
Priority
The instant application is a 371 National Stage Entry of PCT/US2021/047100 filed on August 23, 2021 which claims benefit to domestic provisional application No. 63/094,621 filed on October 21, 2020.
Response to RCE
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible
for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has
been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37
CFR 1.114.
Status of Claims
Acknowledgement is made of amended (1-3), previously presented (4-19) claims filed July 24, 2026. Claims 1-19 are pending in instant application.
Response to Arguments
Applicant's arguments filed July 24, 2026 have been fully considered but they are not persuasive.
Regarding unexpected results, it is the Examiner’s understanding that Applicant alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed 2/23/26 at p. 12-23). However, to establish unexpected results, the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP § 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
If Applicant means to allege the existence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 based upon instant “Example 1” (see, e.g., Reply filed 7/24/26at p. 12 ¶7, see also instant spec. at p. 49-50 “SMV32”) this is also not persuasive because the requirements of MPEP § 716.02 have not been satisfied. Specifically,
I. MPEP § 716.02(b) is not satisfied because no evidence of statistical significance has been placed on record.
II. MPEP § 716.02(d) is not satisfied because such proffered evidence is not commensurate in scope with the instant claims with respect to:
i) covering a diverse and representative range of cancer species (see instant spec. at. p. 49 line 11 “colorectal tumor line” and p. 50 lines 4-5 “PD-1 blockade resistant tumor model Lewis Lung Carcinoma”) vs instant claims “treating cancer”)
ii) covering a diverse and representative range of species of Formula I and immunotherapies (see instant Fig 1, noting only SV-23 and SV-32 perform better than PPV, and instant Figs 3-5 noting only one species of Formula I, SMV-32, is tested in combination with one immunotherapy, one PD-1 blocking antibody).
III. MPEP § 716.02(e) is not satisfied because no comparison to the closest prior art is provided or explained.
Accordingly, for at least these reasons, the proffered data provided in the instant specification is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP § 716.02 at this time.
Regarding increase tumor growth, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “increase tumor growth delay in immunotherapy resistant tumors”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding the double patenting rejection, the Examiner appreciates Applicant’s acknowledgement that it is difficult to compare the scope of claims in copending applications undergoing prosecution. Regrettably, the Examiner cannot hold the rejection in abeyance until allowable subject matter has been determined. The rejection has been modified in light of claim amendments in the copending application.
In light of Applicant’s amendments filed July 24, 2026, the previously applied rejections have been modified. New rejections have also been applied.
New Rejections
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 1-2, 6-19 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 claims 1-2, 6-19 and “can be”, Claim 1 recites “E, G, H can be independently selected”. The metes and bounds of the claim are unclear because it is ambiguous if the limitation is required or optional. For the purposes of applying art, claim 1’s “can be” is interpreted as “E, G, H are independently selected from”.
Claim 1 recites “can be” in multiple instances. The above interpretation of “are” instead of “can be” is applied in each instance.
Similarly, claim 2 recites multiple instances of “can be” and the above interpretation is applied.
Dependent claims 6-19 do not resolve this issue of indefiniteness and are thus included in instant rejection.
Further regarding claims 1-2, 6-19 and “independently”, it is unclear if by “independently selected from” in claim 1 is referring to among E, G, and H, or for each instance of E, G, and H. For Example, it is unclear if compound 19 of claim 3 is encompassed by instant Formula I. Compound 19 has one E as N, but the other two E’s of Formula I are C. Claim 1 states “wherein at least one of E, G, and H are N, O, are S, so it is unclear if by E being N, all instances of E must N or not. For the purposes of applying art, it is assumed applicant meant “each instance of E, G, and H are independently selected from C, N, O, and S, wherein at least one instance of E, G, and H is selected from N, O, and S”.
Claim 3 Instant Formula I
Claim 1 Formula I
PNG
media_image1.png
84
126
media_image1.png
Greyscale
PNG
media_image2.png
276
248
media_image2.png
Greyscale
Similarly, claim 2 recites the same ambiguous limitation and the above interpretation is applied.
Dependent claims 6-19 do not resolve this issue of indefiniteness and are thus included in instant rejection.
Further regarding claim 13, claim 13 recites the limitation “the composition". There is insufficient antecedent basis for this limitation in the claim.
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 3-5 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.
Claims 3-5 list species not encompassed by Formula I of claim 1 from which they depend. The claims include species wherein E, G, and H are all C, whereas claim 1 states “wherein at least one of E, G, and H is selected from N, O, and S”. For example, in the exemplary species below, no instance of E, G, or H is N, O, or S.
Exemplary Species of Claims 3-4
Claim 1 Formula I
PNG
media_image3.png
122
176
media_image3.png
Greyscale
PNG
media_image2.png
276
248
media_image2.png
Greyscale
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 § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4, 6-7, 10, 18 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0233950 A1 to Jung et. al.1 in view of Benej et. al.2
Regarding claim 1, 6, 10 and a method of treating cancer, Jung teaches quinazoline compounds such as CAS# 947688-58-6 (see Jung at p. 23 ¶[0362] and p. 35 “Example 1”) for treating solid tumors (see Jung at p. 1 ¶[0001]). CAS# 947688-58-6 reads on Formula I when R1 is C1-C6 alkyl specifically methyl, R2 is C1-C6 alkoxy specifically methoxy, A is absent, D is O, one of E is N and the other two are C, one of G is N and the other is C, H is C, R3/R7 are H, one of are R4/R6 is absent because one G is N and the other is H, R5 is a C1-C6 alkoxy specifically CH2COOH.
Jung
CAS# 947688-58-6
Instant Formula I
PNG
media_image4.png
132
302
media_image4.png
Greyscale
PNG
media_image5.png
217
195
media_image5.png
Greyscale
Jung teaches the anticancer treatment can be in combination with radiotherapy or chemotherapy (see Jung at p. 33 ¶[0514]) such as an immunotherapy (see Jung at p. 33 right col. “(ix) immunotherapy…”).
Regarding claim 2 and a composition, Jung teaches compositions that comprise both the quinazoline compound and an additional anti-cancer agent (see Jung at p. 34 [0517]). Jung also teaches a composition comprising a quinazoline compound and a diluent or carrier (see Jung claim 10).
Regarding claim 7 and cancer types, Jung teaches treating lung cancer (see Jung at p. 32 ¶[0504]).
Regarding claim 18 and chemotherapy, Jung teaches the anticancer treatment can be in combination with radiotherapy or chemotherapy (see Jung at p. 33 ¶[0514]) such as an another antiproliferative/antineoplastic drug such as cisplatin, reading on chemotherapeutic drug (see Jung at p. 33 left col. ¶[0514]) “(i)”).
The prior art differs from the instant claims as follows: while Jung teaches a method of treating cancer with a compound of Formula I and an immunotherapy, Jung does not specify the quinazoline compound can inhibit mitochondrial oxygen consumption.
However,
Benej teaches papaverine inhibits mitochondrial complex I, which results in increased oxygenation and enhanced radiation response in tumors (see Benej at Abstract). Benej teaches the anticancer strategy of metabolic radiosensitization, a therapeutic concept that targets the metabolic demand for oxygen by down regulating mitochondrial oxidative metabolism (see Benej at p. 10759 right col. “Discussion”).
Jung
CAS# 947688-58-6
Papavarine
Instant Formula I
PNG
media_image4.png
132
302
media_image4.png
Greyscale
PNG
media_image6.png
152
256
media_image6.png
Greyscale
PNG
media_image5.png
217
195
media_image5.png
Greyscale
Regarding claims 3-4, Benej teaches the compound of instant claim 4 as a papaverine derivative (see Benej at p. 10760 Fig 5A SMV-32), and has a mitochondrial IC50 of 7.2 μM (see Benej at p. 1079 left col. ¶2).
Jung
CAS# 947688-58-6
Benej SMV-32
Instant Claim 4
PNG
media_image4.png
132
302
media_image4.png
Greyscale
PNG
media_image7.png
122
188
media_image7.png
Greyscale
PNG
media_image8.png
114
172
media_image8.png
Greyscale
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to an artisan to reasonably expect that by administering CAS# 947688-58-6 in combination with an immunotherapy to a cancer tumor patient (as taught by Jung), that CAS# 947688-58-6 would also inhibit mitochondrial oxygen consumption in a cancer cell, because the prior art teaches a structurally similar antitumor agent, papaverine, inhibits mitochondrial oxygen consumption (as taught by Benej). Alternatively, it would have been obvious to an artisan to improve upon the method of treating a tumor taught by Jung by substituting a quinazoline compound such as CAS# 947688-58-6 for Benej’s SMV-32 (the same as the species of instant claim 4) because they are both papaverine derivatives and structurally similar, and Benej teaches SMV-32 inhibits mitochondrial oxygen consumption, which would help sensitive the tumor.
Furthermore, it is well-within the ordinary skill in art to administer known anticancer treatments to a cancer patient.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 11-12, 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0233950 A1 to Jung in view of Benej as applied to claims 1-4, 6-7, 10, 18 above and in further view of Cook et. al.3
The prior art differs from the instant claims as follows: While Jung and Benej teach treating cancer with a combination of a compound of Formula I and immunotherapy, they do not specify a dosage routine or an immune checkpoint inhibitor.
Regarding instant claims 11-12 and immunotherapy, Cook teaches chemotherapy and immunotherapy are anti-cancer treatments (see Cook at p. 23 “Introduction”). Cook teaches anti-cancer immunotherapies include checkpoint targeting agents such as CTLA-4, PD-1, and PD-L1 inhibitors (see Cook at p. 25 “Combining chemotherapy and checkpoint blockade”).
Regarding instant claims 13-17 and dosage regimens, Cook teaches cancer patients receive treatment cycles (see Cook at p. 26 right col.) and emphasizes the importance of scheduling individual components in chemoimmunotherapy combinations (see Cook at p. 25 right col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding combinations, per MPEP § 2144.06(I), "[i]t 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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It would have been obvious to combine known anti-cancer treatments including the compounds Jung or Benej with chemotherapeutic or immunotherapeutic agents to treat cancer because Cook teaches chemotherapeutic and immunotherapeutic agents are anti-cancerous and can be used in combinations.
Regarding dosage regimens, it would have been obvious to one skilled in the art to arrive at a dosage schedule through routine experimentation because Cook emphasizes the importance of timing when using anti-cancer combinations (see MPEP § 2144.05(II)).
Furthermore, it is well-within the ordinary skill in art to develop a dosing regimen for a patient with a known drug or combination of known drugs.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0233950 A1 to Jung in view of Benej as applied to claims 1-4, 6-7, 10, 18 above and in further view of Remington et. al.4
The prior art differs from the instant claims as follows: While Jung and Benej teach treating cancer with a combination of a compound of Formula I and immunotherapy, they do not specify an administration route.
However,
Regarding claim 18 and administration routes, Remington teaches various methods of formulating for administration routes (see Remington at p. xxi Contents and e.g. p.837 Chapter 42 “Intravenous Admixtures”).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding administration routes, it would have been obvious to one skilled in the art to have formulated the composition for an administration route because in order to treat a patient, the composition must be administered and Remington teaches formulations for different administration routes (see MPEP § 2144.05(II)).
Furthermore, it is well-within the ordinary skill in art to formulate a composition for an intended administration route.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 6-12, 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 6638939 B2 to Uckun et. al.5 as evidenced by Rodriguez-Abreu et. al.6 in view of Cook.
Regarding claims 1, 2, 7, 9, 18, and compounds of Formula I or compositions, Uckun teaches quinazoline compounds and compositions thereof containing amine linker that reads on instant Formula I for treating cancer such as leukemia, breast cancer, or brain tumors (see Uckun at Abstract, at cols. 59-60, and claims 1, 9, 11-12), wherein Uckun R1 reads on instant R1 and R2 specifically R2 is alkoxy, Uckun Ra and Rb corresponds to instant R3-R7, instant E is N in the fused ring and instant E, G, H are C in the monocyclic ring specifically phenyl and A-D is NR’, specifically NH (compare Uckun claim 1 with instant claim 1 Formula I).
Regarding claims 6 and 8, Rodriguez-Abreu explains leukemia is a hematological cancer (see Rodriguez-Abreu at p. i3 “incidence rates”), and one skilled in the art would readily appreciate a brain tumor is a solid tumor.
Uckun General Formula
Instant Formula I
PNG
media_image9.png
73
134
media_image9.png
Greyscale
PNG
media_image5.png
217
195
media_image5.png
Greyscale
The prior art differs from the instant claims as follows: While Uckun teaches compounds of Formula I for treating cancer, App’989 does not specify further combining with immunotherapy or chemotherapy.
Regarding instant claims 1, 10-12, 18 and combinations, Cook teaches chemotherapy and immunotherapy are anti-cancer treatments (see Cook at p. 23 “Introduction”). Cook teaches anti-cancer immunotherapies include checkpoint targeting agent such as CTLA-4, PD-1, and PD-L1 inhibitors (see Cook at p. 25 “Combining chemotherapy and checkpoint blockade”).
Regarding instant claims 13-17 and dosage regimens, Cook teaches cancer patients receive treatment cycles (see Cook at p. 26 right col.), and emphasizes the importance of scheduling individual components in chemoimmunotherapy combinations (see Cook at p. 25 right col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding combinations, per MPEP § 2144.06(I), "[i]t 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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It would have been obvious to combine known anti-cancer treatments including the compounds of Uckun with chemotherapeutic or immunotherapeutic agents to treat cancer because Cook teaches chemotherapeutic and immunotherapeutic agents are anti-cancerous and can be used in combinations.
Regarding dosage regimens, it would have been obvious to one skilled in the art to arrive at a dosage schedule through routine experimentation because Cook emphasizes the importance of timing when using anti-cancer combinations.
Furthermore, it is well-within the ordinary skill in art to develop a dosing regimen for a patient with a known drug or combination of known drugs.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Uckun as evidenced by Rodriguez-Abreu in view of Cook as applied to claims 1-2, 6-12, 13-18 above and in further view of Remington.
The prior art differs from the instant claims as follows: While Uckun teach treating cancer with a combination of a compound of Formula I and immunotherapy, they do not specify an administration route.
However,
Regarding claim 18 and administration routes, Remington teaches various methods of formulating for administration routes (see Remington at p. xxi Contents and e.g. p.837 Chapter 42 “Intravenous Admixtures”).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding administration routes, it would have been obvious to one skilled in the art to have formulated the composition for an administration route because in order to treat a patient, the composition must be administered and Remington teaches formulations for different administration routes (see MPEP § 2144.05(II)).
Furthermore, it is well-within the ordinary skill in art to formulate a composition for an intended administration route.
Claim(s) 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Uckun in as evidenced by Rodriguez-Abreu in view of Cook as applied to claims 1-2, 6-12, 13-18 above and in further view of Popp et. al.7 and Patani et. al.8
Regarding claim 4, Uckun teaches compound 25 (see Uckun at col. 37) wherein the phenyl is a fused ring system and contemplates no substituents (see Uckun claim 5).
Uckun Compound 25
Instant Exemplary Compound
Claim 4
PNG
media_image10.png
176
335
media_image10.png
Greyscale
PNG
media_image11.png
90
140
media_image11.png
Greyscale
The prior art differs from the claims as follows: While Uckun teaches compounds of instant Formula I, Uckun does not teach wherein the A-D linker is other than NH.
However,
Regarding instant linkers A and D, Popp teaches papaverine derivatives Formulas I-III wherein A-D is CH2, CHOH, or C=O (see Popp at p. 3773).
Instant Formula I
PNG
media_image5.png
217
195
media_image5.png
Greyscale
Uckun General Formula
Popp Formulas I-III
Instant Exemplary Compound 17
Claim 3
PNG
media_image9.png
73
134
media_image9.png
Greyscale
PNG
media_image12.png
108
335
media_image12.png
Greyscale
PNG
media_image13.png
70
109
media_image13.png
Greyscale
Popp even teaches compounds that differ only by -CH2- from instant (see Popp at 3773 and below).
Popp Formula I
Instant Exemplary Compound Claim 3
PNG
media_image14.png
145
134
media_image14.png
Greyscale
PNG
media_image15.png
60
148
media_image15.png
Greyscale
Regarding -CH2- for -NH-, Patani teaches -NH- and -CH2- bioisosteric linkers result in analogues which retain activity (see Patani at p. 3156 right col. ¶1).
Regarding claim 5, Popp teaches an isomer of instant claim 5 (see Popp at p. 3773 and below).
Popp Formula II
Instant Exemplary Compound
Claim 5
PNG
media_image16.png
145
129
media_image16.png
Greyscale
PNG
media_image17.png
69
140
media_image17.png
Greyscale
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding linker changes, given that the Popp and Uckun’s teachings involve compounds that share core structural features and fall within the general class of papaverine derivatives (see also instant claim 3), a person of ordinary skill in the art would combine the teachings of Popp and Uckun by replacing NH with CH2 or CHOH or C=O to arrive at a claimed compound for treating cancer, because Uckun teaches the cores are for treating cancer, Popp teaches they are suitable linkers for papaverine derivatives, and additionally because the CH2 for NH approach is known to retain activity as taught by Patani.
Regarding changes in -CH2-, per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because compounds which are homologs, compounds differing e.g. by -CH2- groups, are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (see, e.g., MPEP § 2144.09(I)-(II)). In addition, the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740.
Regarding isomers, MPEP § 2144.09(II) also states position isomers are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Furthermore, it is well-within the ordinary skill in art to make known modifications to a known compound.
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 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15-17, 19-25, 27, 29 of copending Application No. 17/262,9899 (reference application) in view of Cook et. al.10 and Remington et. al.11 as evidenced by Rodriguez-Abreu. Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding a compound of Formula I and claims 1-6, App’989 teaches compounds of Formula I with overlapping structural limitations (see App’989 claims 1, 15-17, 19-25, 27) and composition comprising said compounds (see App’989 claim 29).
App’989 Formula I
Instant Formula I
PNG
media_image18.png
240
205
media_image18.png
Greyscale
PNG
media_image19.png
242
199
media_image19.png
Greyscale
Regarding a method and claims 1-9, per MPEP §804(II)(B)(1), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). In particular, 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. App’989 discloses the utility of treating hypoxic tumors (see App’989 at p. 2 lines 6-7) including cancerous tissues such as colorectal, breast, bladder, brain, cervical, gastrointestinal, genitourinary, head and neck, lung, pancreatic, prostate, renal, skin, or testicular (see App ‘989 at p. 4 lines 7-16), or sarcomas, leukemias, lymphomas, or multiple myelomas (see App’989 at p. 40 lines 15-30). Rodriguez-Abreu explains leukemia and lymphoma are hematological cancers (see Rodriguez-Abreu at p. i3 “incidence rates”).
The copending claims differ as follows: While App’989 claims the same compounds for the same uses, App’989 does not specify further combining with immunotherapy or chemotherapy, nor specify a dosing regimen.
However,
Regarding instant claims 1, 10-12, 18 and combinations, Cook teaches chemotherapy and immunotherapy are anti-cancer treatments (see Cook at p. 23 “Introduction”). Cook teaches anti-cancer immunotherapies include checkpoint targeting agent such as CTLA-4, PD-1, and PD-L1 inhibitors (see Cook at p. 25 “Combining chemotherapy and checkpoint blockade”).
Regarding instant claims 13-17 and dosage regimens, Cook teaches cancer patients receive treatment cycles (see Cook at p. 26 right col.), and emphasizes the importance of scheduling individual components in chemoimmunotherapy combinations (see Cook at p. 25 right col. ¶2).
Regarding claim 18 and administration routes, Remington teaches various methods of formulating for administration routes (see Remington at p. xxi Contents and e.g. p.837 Chapter 42 “Intravenous Admixtures”).
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the copending application for at least the following reason(s):
Regarding combinations, per MPEP § 2144.06(I), "[i]t 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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It would have been obvious to combine known anti-cancer treatments including the compounds of App’989 with chemotherapeutic or immunotherapeutic agents to treat cancer because Cook teaches chemotherapeutic and immunotherapeutic agents are anti-cancerous and can be used in combinations.
Regarding dosage regimens or administration routes, it would have been obvious to one skilled in the art to arrive at a dosage schedule through routine experimentation because Cook emphasizes the importance of timing when using anti-cancer combinations, and to have formulated the composition for an administration route because in order to treat a patient, the composition must be administered and Remington teaches formulations for different administration routes (see MPEP § 2144.05(II)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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, KORTNEY KLINKEL can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Published September 17, 2009. Hereinafter Jung.
2 Benej et. al. "Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism" PNAS 2018, 115, 42, 10756-10761. DOI: 10.1073/pnas.1808945115. Hereinafter Benej.
3 Cook et. al. "Chemotherapy and immunotherapy: mapping the road ahead" Current Opinion in Immunology 2016, 39, 23–29. DOI: 10.1016/j.coi.2015.12.003. Hereinafter Cook. Cited in a previous Office Action.
4 Remington's Pharmaceutical Sciences (21st Ed) New York, NY: Lippincott Williams and Wilkins 2005. Hereinafter Remington. Cited in a previous Office Action.
5 Patented October 28, 2003. Hereinafter Uckun.
6 Rodriguez-Abreu et. al. “Epidemiology of hematological malignancies” Annals of Oncology 2007, 18, i3-i8. DOI: 10.1093/annonc/mdl443. Hereinafter Rodriguez-Abreu.
7 Popp et. al. "Synthesis of Papaverine, Papaverinol, and Papaveraldine from Reissert Compounds" J. Am. Chem. Soc. 1957, 79, 14, 3773-3777. DOI: 10.1021/ja01571a043. Hereinafter Popp.
8 Patani et. al. "Bioisosterism: A Rational Approach to Drug Design" Chem Rev 1996 96, 8, 3147-3176. DOI: 10.1021/cr950066q.
9 371 of PCT/US2019/043082 filed July 23, 2019 claiming benefit of PRO 62/702,201 filed July 23, 2018. Hereinafter App’989.
10 Cook et. al. "Chemotherapy and immunotherapy: mapping the road ahead" Current Opinion in Immunology 2016, 39, 23–29. DOI: 10.1016/j.coi.2015.12.003. Hereinafter Cook.
11 Remington's Pharmaceutical Sciences (21st Ed) New York, NY: Lippincott Williams and Wilkins 2005. Hereinafter Remington.
Prosecution Insights