DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment and Status of the Claims
The amendments filed on March 6, 2026 have been entered. Claims 1-9, 15-18, 20, 21, 23, 25, 26, 31 are pending. Claims 10-14, 19, 22, 24, 27-30, and 32 are cancelled. Examiner previously required a restriction (dated April 10, 2025). In response, Applicant elected, without traverse, Group I which now encompasses claims 1-9, 15-18, and 20. Accordingly, claims 21, 23, 25, 26, and 31 are withdrawn.
Withdrawn Rejections/Objections
Applicant is notified that any outstanding rejection/objection that is not expressly maintained in this office action has been withdrawn or rendered moot in view of applicant's amendments and/or remarks.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of PCT/US2021/035524, filed on June 02, 2021. This application also claims the benefits of U.S. Provisional Application No. 63/033,502, filed on June 02, 2020.
Election/Restrictions
As a reminder, Applicant elected, without traverse, Group (I) which now corresponds to claims 1-9, 15-18, and 20. Applicant also elected the compound of Formula (IV), which is artemisinin, without traverse, and is now embodied by claims 1-2, 5-9, 15-18, and 20 of Group (I). The elected species, artemisinin, was found in the prior art.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections - Informalities
Claims 2-4, 6-8, and 15-18 are objected to because of the following informalities:
For consistency and to avoid a 112(a)-scope of enablement issue, claim 2 should read:
“The anti-cancer agent according to claim 1, wherein the at least one compound comprising at least one 1,2,4-trioxane moiety is selected from those of
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and, where applicable, a pharmaceutically acceptable salt of the compound of formula (II)…
To avoid a 112(a)-scope of enablement issue, in claim 2, all limitations starting from “wherein in formula (I)” all the way to right before “And in formula (II)” should be removed.
For consistency, in claim 2:
“And in formula (II)…” should be replaced with “wherein in formula (II)…”
To avoid a 112(a)-scope of enablement issue, claim 2 should also read:
“…R2 is a C1-C6 alkyl or –(CO)R3 and R3 is C1-C6 alkyl that is substituted once with -COOH”
Note: all other limitations pertaining to formula (II) on pg. 4 and 5 of the most recently amended claim set should be removed.
For consistency, claims 3 and 4 should read:
“The anti-cancer agent according to claim 1 wherein the at least one compound comprising at least one 1,2,4-trioxane moiety is selected from… and a pharmaceutically acceptable salt of artesunate.”
For consistency, claim 6 should read:
“…wherein a molar ratio between the at least one compound having at least one 1,2,4-trioxane moiety and the at least one chlorogenic acid present in the combination is between 2 and 0.002.”
For consistency, claim 7 should read:
“…wherein the at least one compound comprising at least one 1,2,4-trioxane moiety is obtained…”
For consistency, claim 8 should read:
“…further comprising an extract of Artemisia annua.”
For consistent claim formatting, in claims 15-17:
“Pharmaceutical compositions…” should read “A pharmaceutical composition…”
For consistency, claim 17 should further read:
“…wherein the at least one additional therapeutic agent is selected from the group of…”
For consistency, in claim 18:
“Kit comprising:” should read “A kit comprising:”
Appropriate correction is required.
Examiner has identified numerous claim informalities. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the claims.
Claim Objections – Substantial duplicates
Claims 7 and 9 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. Claims 7 and 9 differ from claim 1 only in reciting that:
the at least one compound comprising at least one 1,2,4-trioxane moiety is obtained via extraction of Artemisia annua (as recited in claim 7) and
the at least one chlorogenic acid is obtained via extraction of coffee or tea (as recited in claim 9).
However, this limitation does not impart any structural distinction to the claimed anti-cancer agent of claim 1.
According to MPEP § 2113, section I:
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production” or in this case, where the product is extracted from.
Therefore, since the anti-cancer agent of claims 7 and 9 are not structurally distinguishable from the anti-cancer agent of claim 1, the additional limitation regarding the source of the at least one compound comprising at least one 1,2,4-trioxane moiety and the at least one chlorogenic acid does not further limit the claimed subject matter. As such, claims 7 and 9 define the same subject matter as claim 1 and are objected to as being substantial duplicates thereof.
Claim 15 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. Claim 15 is directed to pharmaceutical compositions comprising an anti-cancer agent according to claim 1 with no additional components specified. Therefore, the claim language of instant claim 15 suggests that the pharmaceutical compositions can be identical to the anti-cancer agent of instant claim 1. Therefore, claim 15 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a duplicate of the independent claim.
Claim 20 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1.
According to MPEP § 2114, section II:
“‘[A]pparatus claims cover what a device is, not what a device does.’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a ‘recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus’ if the prior art apparatus teaches all the structural limitations of the claim.”
This can also be translated to a product claim. A product claim covers what a product is, not what a product does. Therefore, a claim containing a recitation with respect to the manner in which a claimed product is intended to be employed does not differentiate the claimed product from a prior art product if the prior art product teaches all the structural limitations of the claim. Therefore, instant claim 20 (which is directed to the anti-cancer agent according to claim 1 for use as a medicament for the treatment of cancer or for the prolongation of a subject having cancer) is a substantial duplicate of claim 1.
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).
-------------------------------------Maintained 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.
Claim 18 is 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 18 still recites the limitation "pharmaceutical composition according to claim 1” in item (c) of claim 18:“…(c) instructions for using the anti-cancer agent or pharmaceutical composition according to claim 1 and the additional therapeutic agent.”
Claim 1 does not recite “a pharmaceutical composition.” Therefore, 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.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Instant claim 15 is still directed to pharmaceutical compositions comprising an anti-cancer agent according to claim 1 with no additional components specified. Therefore, the claim language of instant claim 15 suggests that the pharmaceutical compositions can be identical to the anti-cancer agent of instant claim 1. Therefore, claim 15 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a duplicate of the independent claim.
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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 8, and 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because they encompass compounds that are a product of nature and, therefore, is not patentable.
Specifically, the prior art teaches that the extract of the Artemisia annua plant naturally contains artemisinin (instant formula IV as shown in claim 2), artesunate (instant formula IIb as shown in claim 3), 3-caffeoylquinic acid (same as 3-O-caffeoylquinic acid), 4-caffeoylquinic acid (same as 4-O-caffeoylquinic acid), 5-caffeoylquinic acid (same as 5-O-caffeoylquinic acid), 3,4-di-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, and 4,5-di-caffeoylquinic acid among other compounds (pg. 3, Figure 1 of Suberu, J. O. et al. PLoS ONE 2013, 8, e80790.).
Note on 35 USC § 102 and § 103 Rejections
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-9, 15-17, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Suberu, J. O. et al. (Suberu) (Suberu, J. O. et al. Anti-Plasmodial Polyvalent Interactions in Artemisia annua L. Aqueous Extract – Possible Synergistic and Resistance Mechanisms. PLoS ONE 2013, 8, e80790.)
Suberu teaches that the extract of the Artemisia annua plant naturally contains artemisinin (instant formula IV as shown in claim 2), artesunate (instant formula IIb as shown in claim 3), 3-caffeoylquinic acid (same as 3-O-caffeoylquinic acid), 4-caffeoylquinic acid (same as 4-O-caffeoylquinic acid), 5-caffeoylquinic acid (same as 5-O-caffeoylquinic acid), 3,4-di-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, and 4,5-di-caffeoylquinic acid among other compounds (pg. 3, Figure 1; reads on instant claims 1-5, 7-9, 15, and 20; Note: instant claims 7, 9, 15 and 20 are substantial duplicates of instant claim 1).
Specifically, 1 L of Artemisia annua tea contains the following components at the indicated concentrations (pg. 5, Table 1):
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In 1 L of Artemisia annua, there is on average 47.5 mg of artemisinin (equivalent to 0.000168 mol) and 72.0 mg of 3-caffeoylquinic acid (equivalent to 0.000203 mol). Therefore, the mole ratio of artemisinin to 3-caffeoylquinic acid in 1 L of Artemisia annua tea is 0.000168/0.000203 = 0.828 (which is between 2 and 0.002; reads on instant claim 6).
Su, X.-Z. et al. (Su) (Su, X.-Z. et al. The discovery of artemisinin and the Nobel Prize in Physiology or Medicine. Sci China Life Sci 2015, 58, 1175-1179.)
Su teaches that in 1972, Professor Tu discovered artemisinin (structure shown in instant formula IV in claim 2) and a method to extract the compound from the Artemisia annua plant (pg. 1176, right col., section 4.1, paragraph (2); reads on instant claim 7).
Zhao, W. et al. (Zhao) (Zhao, W. et al. Identification and purification of novel chlorogenic acids in Artemisia annua L. Journal of Experimental Biology and Agricultural Sciences 2015, 3, 415-422.)
Zhao teaches how to isolate and purify chlorogenic acids from Artemisia annua extract (reads on instant claim 9). The extract was obtained by combining 1 g of the Artemisia annua plant with water under ultrasonication for 1 hour at 50oC (pg. 416, last sentence of section 2.1 and entirety of section 2.2). In other words, the extract was obtained by making Artemisia annua tea. In Zhao, ethanol was also included into the mixture since a ratio of 70:30, v/v of ethanol : water is the optimal solvent to use to extract chlorogenic acids from Artemisia annua (pg. 419, right col., 1st paragraph, 4th to last and 3rd to last sentence).
Wang, H. et al. (CN103251585A; published August 21, 2013)
Wang discloses pharmaceutical compositions (English translation of para. 0134-0138, shown below) comprising of dihydroartemisinin (see instant formula III of claim 2 for structure) with either gemcitabine or carboplatin (reads on instant claims 16 and 17).
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Wang further discloses that:
“artemisinin combined with gemcitabine had a significant apoptosis-promoting effect on HepG2 and Hep3B cells [i.e., liver cancer cell lines], and the combination of the two drugs showed a synergistic effect” (English-translated document, pg. 48, lines 5-7)
and
“[t]he combined use of DHA [i.e., dihydroartemisinin] and CBP [i.e., carboplatin] synergistically promoted the apoptosis of OVCAR-3 cells [i.e., ovarian cancer cell line] 24 hours later” (English-translated document, pg. 48, lines, 8-9) (reads on instant claim 20).
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.
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.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over:
Feltquate et al. (Feltquate) (WO2015176033A1; published November 19, 2015) and
Slezakova et al. (Slezakova) (Slezakova, S. et al. Anticancer Research 2017, 37, 5995-6003.)
Feltquate discloses a kit for treating a subject afflicted with a lung cancer, the kit comprising (claim 48: pg. 102, last line and pg. 103):
A dosage of an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to the PD-1 receptor and inhibits PD-1 activity,
A dosage of another anti-cancer agent such as a platinum-based doublet chemotherapy, and
Instructions for using the anti-cancer agent and the other anti-cancer agent.
Feltquate does not disclose artemisinin or an artemisinin derivative being used as an anti-cancer agent. Slezakova is relied upon for this disclosure.
Slezakova summarizes the anticancer properties of artemisinin and its derivatives (i.e., ARTs) that have been previously reported in multiple preclinical and clinical studies (pg. 6001, “Conclusion and Future Perspectives” section, 2nd sentence). Slezakova also states that the “chemosensiting effect of artesunate [i.e., compound of instant formula (IIb)] and dihydroartemisinin [i.e., compound of instant formula (III)] suggests the use of ARTs as an add-on therapy in combination with conventional chemotherapeutics” (pg. 6001, “Conclusion and Future Perspectives” section, 2nd to last sentence).
Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to modify the kit of Feltquate by replacing the anti-cancer agent (i.e., the antibody or an antigen-binding portion thereof) in Feltquate with the anti-cancer agent disclosed in the instant application (e.g., artemisinin, artesunate, or dihydroartemisinin). One of ordinary skill in the art would have been motivated to make such a modification as Slezkova clearly states the use of ARTs as combination (add-on) therapies with conventional chemotherapeutics (such as a platinum-based doublet chemotherapy as disclosed in Feltquate), thereby providing a reasonable expectation that such agents could be used in a combination kit.
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 1-9, 15, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1, 4-6, 8 and 9 of U.S. Patent Application No. 18/007,990 (‘990) and
Claims 1-11 of U.S. Patent Application No. 19/079,342 (‘342).
Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap between the instant claims and the two claim sets from the co-pending applications.
Specifically, the instant claim set teaches an anti-cancer agent comprising at least one compound having at least one 1,2,4-trioxane moiety or a combination of a) at least one compound having at least one 1,2,4-trioxane moiety and b) at least one chlorogenic acid; wherein the molar ratio between the compound or the compounds having at least one 1,2,4- trioxane moiety and the chlorogenic acid or chlorogenic acids present in the combination is between 2 and 0.002; wherein the compound comprising at least one 1,2,4-trioxane moiety are obtained via extraction of Artemisia annua and the at least one chlorogenic acid is obtained via extraction of coffee or tea.
It would have been obvious to a person of ordinary skill in the art to obtain the instant anti-cancer agent because ‘990 teaches a composition that encompasses the anti-cancer agent disclosed in the instant application. The composition of ‘990 comprises a) artemisinin (i.e., the compound of instant formula (IV)) and b) at least one chlorogenic acid; wherein the molar ratio between artemisinin and the chlorogenic acid or chlorogenic acids present in the combination is between 2 and 0.002; wherein the artemisinin is obtained via extraction of Artemisia annua.
It would have also been obvious to a person of ordinary skill in the art to obtain the instant composition because the claim set of ‘342 is drawn to an anti-cancer agent that is a species of the anti-cancer agent disclosed in the instant claim set. The anti-cancer agent of ‘342 comprises a) at least artemisinin and b) at least one chlorogenic acid; wherein the molar ratio between artemisinin and the chlorogenic acid or chlorogenic acids present in the combination is between 2 and 0.002; wherein the anti-cancer agent is an extract of Artemisia annua and coffee.
---------------------------Rejections necessitated by the amended claim set---------------------------
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.
Claim 2 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “n is an integer of either more than 1”, and the claim also recites “n is an integer… 2 to 10; 2,3 or 4; or 2 or 3” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
------------------------------------- Added Rejections -------------------------------------
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 5-9, 15-18, and 20 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 the following:
(Enabled elements)
An anti-cancer agent comprising
at least one compound having at least one 1,2,4-trioxane moiety wherein the 1,2,4-trioxane moiety is selected from the group consisting of:
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wherein in formula (II), R2 is a C1-6 alkyl or –(CO)R3
wherein R3 is C1-6 alkyl that is substituted once with -COOH
OR
or a combination of a) at least one compound having at least one 1,2,4-trioxane moiety and b) at least one chlorogenic acid
wherein the at least one compound having at least one 1,2,4-trioxane moiety is selected from the group consisting of:
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wherein in formula (II), R2 is a C1-6 alkyl or –(CO)R3
wherein R3 is C1-6 alkyl that is substituted once with -COOH
and wherein the at least one chlorogenic acid is selected from the group consisting of 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3-O-ferruoylquinic acid, 4-O-ferruoylquinic acid, 5-O-ferruoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid.
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above.
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 and use the invention commensurate in scope with these claims.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed to make and use the invention based on the content of the disclosure, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims anti-cancer agents comprising 1,2,4-trioxane compounds and anti-cancer agents comprising combinations comprising 1,2,4-trioxane compounds and chlorogenic acids. The invention further provides pharmaceutical compositions comprising such anti-cancer agents, kits comprising the same as well as methods and treatment regimens of using the aforementioned anti-cancer agents, pharmaceutical compositions and kits in the treatment and prevention of cancer and for prolonging survival of subjects having cancer, in particular ovarian cancer or lung cancer.
State of the prior art
See the “Claim Rejections - 35 USC § 102” and “Claim Rejections - 35 USC § 103” sections above.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in medicinal chemistry and organic synthesis/extraction techniques and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The presence or absence of working examples
The instant specification provides working examples limited to a single compound, artesunate, as the representative compound having the 1,2,4-trioxane moiety.
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
While the instant examples provide a motivation to have at least artesunate (i.e., the at least one compound having at least one 1,2,4-trioxane moiety) in the claimed anti-cancer agent, the presence of a single working example is insufficient to reasonably enable the full scope of the genus, particularly where the genus encompasses compounds with substantial structural variability such as those defined by formulae (I) and (II) in claim 2. However, the disclosure is considered enabling for a compound having at least one 1,2,4-trioxane moiety, wherein the compound is:
Artesunate (i.e., instant formula IIb), as expressly exemplified,
A compound having a structure sufficiently similar to artesunate, insofar as artesunate serves as a representative species of that subset of the genus (i.e., a compound having the enabled elements listed above), or
One of the specifically disclosed compounds identified by Applicant (i.e., compounds of formulae (III), (IV), or (V)).
The amount of direction or guidance present and the quantity of experimentation needed to make and use the invention based on the content of the disclosure
The specification provides limited direction or guidance regarding which substituents within the broad definitions of formulae (I) and (II) (as recited in instant claim 2) will yield compounds that are anti-cancer agents or a component of an anti-cancer agent. Although the specification explicitly lists additional specific compounds (i.e., compounds of formulae (III), (IV), and (V)) that could be incorporated in the presently claimed anti-cancer agent, these compounds are not demonstrated in the working examples. However, the explicit disclosure of these specific structures provides some degree of guidance, such that a POSITA would understand that compounds structurally similar to artesunate (see enabled elements above), including the specific compounds of formula (III), (IV), and (V), may be suitable for use in the claimed compositions.
The instant specification does not provide sufficient guidance to allow a POSITA to determine across the full breadth of substituent combinations permitted by the claims, which compounds will retain the necessary activity nor does it provide guidance on how structural variation impacts activity.
The instant specification also does not provide sufficient guidance to enable one of ordinary skill in the art to make an anti-cancer agent comprising at least one compound comprising at least one 1,2,4-trioxane moiety (that are outside the scope of the enabled elements listed above) with at least one chlorogenic acid (that is outside the scope of the enabled elements listed above) to achieve the anticancer activity disclosed in the instant specification. The instant specification also does not provide sufficient guidance on how varying the chlorogenic acid influence the resulting activity.
The breadth of the claims
The claims are broad insofar as the instant claims recite an anti-cancer agent comprising at least one compound having at least one 1,2,4-trioxane moiety or a combination of a) at least one compound having at least one 1,2,4-trioxane moiety and b) at least one chlorogenic acid wherein the 1,2,4-trioxane moiety-containing compound and/or the chlorogenic acid can possess a structurally diverse range of chemical groups.
Claims 2, 5-9, 15-18, and 20, which are dependent on claim 1, are also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above.
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.
Claim 2 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “M is hydrogen… or a primary, secondary, tertiary or quaternary organic ammonium ion…” and the claim also recites “in particular those of formula [N(C1-C18-alkyl)sHt]+ wherein s is 1, 2, 3, or 4 and t is (4-s)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 7, 9, and 20 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 7 and 9 differ from claim 1 only in reciting that:
the at least one compound comprising at least one 1,2,4-trioxane moiety is obtained via extraction of Artemisia annua (as recited in claim 7) and
the at least one chlorogenic acid is obtained via extraction of coffee or tea (as recited in claim 9).
However, this limitation does not impart any structural distinction to the claimed anti-cancer agent of claim 1.
According to MPEP § 2113, section I:
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production” or in this case, where the product is extracted from.
Therefore, since the anti-cancer agent of claims 7 and 9 are not structurally distinguishable from the anti-cancer agent of claim 1, the additional limitation regarding the source of the at least one compound comprising at least one 1,2,4-trioxane moiety and the at least one chlorogenic acid does not further limit the subject matter of the claim upon which it depends and is a substantial duplicate of claim 1.
Additionally, according to MPEP § 2114, section II:
“‘[A]pparatus claims cover what a device is, not what a device does.’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a ‘recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus’ if the prior art apparatus teaches all the structural limitations of the claim.”
This can also be translated to a product claim. A product claim covers what a product is, not what a product does. Therefore, a claim containing a recitation with respect to the manner in which a claimed product is intended to be employed does not differentiate the claimed product from a prior art product if the prior art product teaches all the structural limitations of the claim. Therefore, instant claim 20 (which is directed to the anti-cancer agent according to claim 1 for use as a medicament for the treatment of cancer or for the prolongation of a subject having cancer) is not further limiting claim 1 (i.e., instant claim 20 is not structurally distinguishable from the anti-cancer agent of claim 1) and, in fact, is a substantial duplicate of claim 1.
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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 7, 9, and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because they encompass compounds that are a product of nature and, therefore, is not patentable.
Specifically, the prior art teaches that the extract of the Artemisia annua plant naturally contains artemisinin (instant formula IV as shown in claim 2), artesunate (instant formula IIb as shown in claim 3), 3-caffeoylquinic acid (same as 3-O-caffeoylquinic acid), 4-caffeoylquinic acid (same as 4-O-caffeoylquinic acid), 5-caffeoylquinic acid (same as 5-O-caffeoylquinic acid), 3,4-di-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, and 4,5-di-caffeoylquinic acid (pg. 3, Figure 1 of Suberu, J. O. et al. PLoS ONE 2013, 8, e80790.). Claims 7, 9, and 20, which are substantial duplicates of claim 1, encompasses the extract of the Artemisia annua plant.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624