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 .
DETAILED ACTION
2. Claims 1 – 20 are pending in this application.
Priority
3. This application is a domestic application, filed May 11, 2023, which claims benefit of domestic application 63/365,528, filed May 31, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/31/2024 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in line 15 of page 2. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2, 6, and 9 – 10 are objected to because of the following informalities:
Claim 2, line 3, “where” should read “wherein”.
Claims 2 and 9, lines 3 and 4, respectively, “,” should be inserted immediately after “F”, “methyl”, and “methyl”.
Claim 6, line 3, “,” should be inserted immediately after “(CKD-9).
Claim 10, line 2, “where” should read “wherein”.
Appropriate correction is required.
Claim 7 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Claim 7 has been indicated as being allowable or as containing allowable subject matter because claim 7 require the recitation of “a ketal of 2,2-difluoromethane”. There is no available prior art that teaches this subject matter.
Claim Rejections - 35 USC § 112
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 2 – 7 and 9 – 13 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 2 and 9 recite the anticancer compound, “wherein the CKD comprises
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wherein X is H”. Claims 2 and 9 depend from claim 1, but claims 2 and 9 do not further limit the subject matter of the claim because when X is H, claims 2 and 9 encompass CK, not a derivative of CK. Claims 3 – 7 and 10 – 13, depend from claims 2 and 9, are also rejected because these claims encompass the natural product and they are only limiting the substituents and variables without limiting the anticancer compound to be the derivative of CK only. 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 2 – 7 and 9 – 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite 20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol (CK), which is a national product.
Step 1: Claims 2 – 7 and 9 – 13 recite compounds and compositions of matter, thus, the claims fall into a statutory category of invention under 35 U.S.C. 101.
Step 2A1: The claimed compound in claims 2 and 9
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wherein X is H is CK and not a derivative of CK. It is known in the art that CK is a natural metabolite of ginsenosides, which are active compounds found in ginseng. When, as here, a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation.
The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed in terms of structure, function, and/or other properties, and are evaluated on what is recited in the claim. If the analysis indicates that a nature-based product limitation does not exhibit markedly different characteristics, then that limitation is a product of nature exception. If the analysis indicates that a nature-based product limitation does have markedly different characteristics, then that limitation is not a product of nature exception. MPEP 2106.04(c)(II).
Claiming a natural product that is merely separated from elements found in its natural environment, where the structure of the natural product is not otherwise altered, does not support a conclusion that the isolated product is patent eligible. Ass’n for Molecular Pathology v. Myriad, 569 U.S. 576 at 593-5 (2013) (contrasting cDNA, which is exons-only molecule that is not naturally occurring, from isolated DNA segments because the isolated DNA segments do not contain altered genetic information compared to the gene from which isolated, notwithstanding that the isolated DNA segment was obtained by breaking chemical bonds).
The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. 576 at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the Applicant must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.
The first step in the analysis requires selecting the appropriate natural counterparts to the claimed nature-based products. The appropriate natural counterpart to the claimed isolated compound is the same compound as the natural metabolite of ginsenosides. The second step in the analysis requires identifying appropriate characteristics to compare. In this case, the appropriate characteristics pertain to the chemical nature of the compounds, which ultimately determine their bioactivity.
The analysis requires determining if isolating the claimed natural compound results in the compound having structural, functional, or other properties that are different from the compound as found in their natural setting. While the specification demonstrates evidence that the claimed isolated natural compounds possess certain bioactivity (pp. 10), this activity is based on chemical structure. No evidence is asserted that isolating the claimed natural compound changes the intrinsic bioactivity of the claimed compounds.
Accordingly, claims 2 and 9 as well as the dependent claims 3 – 7 and 10 – 13 recite judicial exceptions, i.e., products of nature.
Step 2A2: This part of the eligibility analysis evaluates whether a claim as a whole integrates the recited judicial exception into a practical application. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. A claim reciting a judicial exception is not directed to the judicial exception if it also recites additional element(s) demonstrating that the claim as a whole integrates the exception into a practical application. One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. In order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of such a limitation is a step of "administering amazonic acid to a patient" or a step of "administering a course of plasmapheresis to a patient." If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. (MPEP 2106.04(d)(2)).
Each of claims 2 – 7 and 9 – 13 are drawn to compound which do not include limitations imposing any particular use of or application of the claimed judicial exceptions, such as a particular treatment or prophylaxis. Accordingly, the compound of claims 2 – 7 and 9 – 13 do not contain additional elements that result in a practical application of the claimed compound, because these claims are drawn to compound rather than applications of the compound.
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim.
The search for an “inventive concept” as required by the Supreme Court in Alice is not the search for a “patentable invention” (which includes satisfying §§ 102, 103 and 112, in addition to 101). An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981. Instead, an "inventive concept" is furnished by an element or combination of elements recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
In this case, the claimed judicial exceptions occur within chemical compound (claims 2 – 7 and 9 – 13). Formulating CK as an anticancer compound is well-understood, routine, and conventional practice. For example, Zhou et al. (Chemical Biology & Drug Design, February 2022, Vol. 99, Issue 2, page 286 – 300, Reference included with PTO-892) teach that CK is a major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo (Abstract).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 2 and 8 – 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Chemical Biology & Drug Design, February 2022, Vol. 99, Issue 2, page 286 – 300, Reference included with PTO-892) in view of Tatsumura et al. (British Journal of Cancer, 1990, Vol. 62, Issue 3, page 436 – 439, Reference included with PTO-892).
a. Regarding claims 1 – 2 and 8 – 9, Zhou et al. teach that ginsenoside compound K (CK) is the major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo. CK exerts anticancer effects via multiple molecular mechanisms, including the inhibition of proliferation, invasion, and migration, the induction of apoptosis an autophagy, and anti-angiogenesis. Some signaling pathways play a significant role in related processes, such as PI3K/Akt/mTOR, JNK/MAKS pathway, and reactive oxygen species (ROS) (Abstract). Zhou et al. teach the chemical structure of CK as well as other ginsenoids (page 285, Figure 1):
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However, Zhou et al. do not teach the compound:
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wherein X is H and R1 are H and R2 is an unsubstituted aromatic group.
Tatsumura et al. teach 4,6-0-Benzylidene-D-glucopyranose (BG), a derivative of benzaldehyde (BA)(Abstract; page 436, Right Col., Figure 1):
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Tatsumura et al. disclose that BG can be clinically useful for the treatment of tumors based on the results obtained. In the study, the lack of toxicity of BG, at least with the size of dose used, is exceptional for anti-tumor agents and widens the future potential use of this drug (page 438, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify CK as taught by Zhou et al. with the incorporation of BG in view of Tatsumura et al. because Zhou et al. teach CK and other derivatives of CK as well as the common position for CK modification and Tatsumura et al. teach BG that is an exceptional anti-tumor agent. It would have been obvious to modify because CK and BG are known separately in the art for the purpose of treating tumor, and it would have been obvious to incorporate BG into CK to treat the same disease. One would have been motivated to modify CK as taught by Zhou et al. with the incorporation of BG in view of Tatsumura et al. because Zhou et al. suggest the location of modification and Tatsumura et al. confirm that BG is lack of toxicity and has anti-tumor properties, thereby, making it an exceptional anti-tumor agent. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify CK as taught by Zhou et al. with the incorporation of BG in view of Tatsumura et al. because Zhou et al. teach the possible location for modifying CK, Tatsumura et al. teach the benefit of BG, and it is well known to incorporate functional moiety with antitumor property to an existing antitumor agent for treating tumor.
Claims 2 – 6 and 10 – 13 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Chemical Biology & Drug Design, February 2022, Vol. 99, Issue 2, page 286 – 300, Reference included with PTO-892) in view of Tatsumura et al. (British Journal of Cancer, 1990, Vol. 62, Issue 3, page 436 – 439, Reference included with PTO-892) as applied to claims 1 – 2 and 8 – 9 above, and further in view of Zhang et al. (Machine Translation of CN101157711A).
b. Regarding claims 2 – 6 and 10 – 13, Zhou et al. and Tatsumura et al. teach the limitation discussed above.
However, these references do not teach the claimed R substituent to be OCH3.
Zhang et al. teach a class of compounds with anti-tumor activity (Abstract), wherein the compounds relate to 4,6-O-benzylidene-β-D-glucopyranoside, which has obvious cytotoxic activity and can be used as an antitumor drug, especially for preparing antitumor drug preparations (page 2, lines 9 – 10). Zhang et al. teach the derivative of 4,6-O-benzylidene-β-D-glucopyranoside
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which has the modifications on the aryl ring as well as the glucopyranoside, wherein R2 is OCH3 (page 2, line 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the BG moiety in the derivative of CK as taught by Zhou et al. and Tatsumura et al. with the substitution of a hydrogen on the aryl ring to OCH3 in view of Zhang et al. because these references teach compounds that have antitumor activity and such modification of BG is known in the art for yielding compound that retains antitumor activity. It would have been obvious for one of ordinary skill in the art to do this because the results of the substitution would have been predictable. As Zhang et al. teach the derivative of 4,6-O-benzylidene-β-D-glucopyranoside that encompass the OCH3 at any location on the aryl ring, one would have performed routine experimentation to discover the best location of the replacement from H to OCH3 for the optimal treatment characteristics. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify the BG moiety in the derivative of CK as taught by Zhou et al. and Tatsumura et al. with the substitution of a hydrogen on the aryl ring to OCH3 in view of Zhang et al. because Zhou et al. and Tatsumura et al. teach CK, the derivatives of CK, and BG are antitumor agent and Zhang et al. teach the possible modification of BG that retains antitumor activity, thereby, such substitution are predicted to retain antitumor activity for treating cancer.
Claims 14 and 16 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Chemical Biology & Drug Design, February 2022, Vol. 99, Issue 2, page 286 – 300, Reference included with PTO-892) in view of Tatsumura et al. (British Journal of Cancer, 1990, Vol. 62, Issue 3, page 436 – 439, Reference included with PTO-892) and Zhang et al. (Machine Translation of CN101115771A) as applied to claims 1 – 6 and 8 – 13 above, and further in view of Hecht et al. (US2012/0148502A1).
c. Regarding claims 14 – 20, Zhou et al., Tatsumura et al., and Zhang et al. teach the limitations discussed above.
However, these references do not teach the method for preparing the CKD.
Hecht et al. teach example 5 (para. [0201]:
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for forming a fused pyranopyran compound, wherein the reaction involves PhCH(OMe)2 as a reagent which provide acetal, DMF as a solvent, and TsOH as a catalyst (para. [0202]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Zhou et al., Tatsumura et al., and Zhang et al. with the reaction for forming a fused pyranopyran compound in view of Hecht et al. to obtain the claimed CKD because Hecht et al. teach the general reaction of transforming a pyranose into a fused pyranopyran compound via acid-catalyzed acetal formation. It would have been obvious to combine the teachings of Zhou et al., Tatsumura et al., and Zhang et al. with the reaction for forming a fused pyranopyran compound in view of Hecht et al. to obtain the claimed CKD because the reaction is known in the art for converting a pyranose into a fused pyranopyran compound. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the teachings of Zhou et al., Tatsumura et al., and Zhang et al. with the reaction for forming a fused pyranopyran compound in view of Hecht et al. to obtain the claimed CKD because the reaction that taught by Hecht et al. is known in the art and the combination of teachings will yield the claimed CKD, which is predictable.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Chemical Biology & Drug Design, February 2022, Vol. 99, Issue 2, page 286 – 300, Reference included with PTO-892) in view of Tatsumura et al. (British Journal of Cancer, 1990, Vol. 62, Issue 3, page 436 – 439, Reference included with PTO-892), Zhang et al. (Machine Translation of CN101115771A), and Hecht et al. (US2012/0148502A1) as applied to claims 1 – 6, 8 – 14, and 16 - 20 above, and further in view of Chemical Book (Chemicalbook.com, 2019, Reference included with PTO-892).
d. Regarding claim 15, the references teach the limitations discussed above.
However, these references do not teach using 2,2-dimethyoxypropane in the reaction for obtaining CKD.
Chemical Book teaches reactions for forming acetals. The formation of acetals are established when 2,2-dimethoxypropane, and alcohol, and a catalytic amount of acid are mixed (page 1, para. 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute PhCH(OMe)2 as taught by Hecht et al. with 2,2-dimethoxypropane in view of Chemical Book for providing acetal group because Chemical Book teach that 2,2-dimethoxypropane is used as a reagent for preparing a variety of acetals. It would have been obvious to substitute PhCH(OMe)2 as taught by Hecht et al. with 2,2-dimethoxypropane in view of Chemical Book for providing acetal group because both PhCH(OMe)2 and 2,2-dimethoxypropane are known separately in the art for the reaction to provide acetal group. It would have been obvious to substitute PhCH(OMe)2 with 2,2-dimethoxypropane as the reagent for the same reaction. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to substitute PhCH(OMe)2 as taught by Hecht et al. with 2,2-dimethoxypropane in view of Chemical Book because Hecht et al. teach the reaction for the formation of acetals that used PhCH(OMe)2 as the reagent and Chemical Book also teaches the same reaction with 2,2-dimethoxypropane as the acetal reagent, thereby, the substitution will yield predictable results.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693