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
Claims 1-20 are pending in the instant application.
Claims 1-20 are being examined on their merits herein.
Priority
The instant application claims priority from U.S. Provisional Patent Application No. 63/524,469, filed on 30 June 2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 June 2024 is acknowledged and considered.
Claim objection
Claims 1, 5, 11 are objected to because the text “compound represented by the structure of formula I” could read –compound of formula I--.
Claims 1, 5, 11 are objected to because they recite “compound […] of formula I, or its enantiomer or racemic mixture thereof”. Formula I, as drawn, is a racemic mixture; therefore, the text should read -- compound […] of formula I, or an enantiomer thereof--.
Claims 4, 8, 13 are objected to because the recitation “R3 and R4 form a dioxolane” should read -- R3 and R4, together with the carbon atoms they are attached to, form a dioxolane--. Support for this recitation is found in Applicant’s Specification, structure in paragraph [0059]
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. Alternatively, the claims could read that R3-R4 is -O-CH2-O- --.
Objection to the Specification
The Specification is objected to because it incorrectly names compound Rac-M at least in paragraphs [0130], [0131], [0132], [0133]
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.
The chemical structure of Rac-M is shown in Fig. 2 and Fig 3. Applicant is invited to identify all instances in the Specification where the compound is named and correct its name.
Claim Rejections - 35 USC § 112
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 4, 8, 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 is drawn to the compound of claim 1, wherein R1 is a hydroxyl group, R2 is a hydrogen, and R3 and R4 form a dioxolane. Yet, claim 1 recites that R3 and R4 are an ethylene oxide, dioxirane, oxetane, dioxetane, dioxolane, dihydrofuran, or furan, which is interpreted to mean that each of R3 and R4 is selected from, for example, dioxolane. As such, there is insufficient antecedent basis for the limitation “R3 and R4 form a dioxolane” of claim 4, in claim 1.
The same analysis applies to claim 8, which depends on claim 5; and to claim 13, which depends on claim 11.
Appropriate correction/clarification is required.
In the interest of compact prosecution, the examiner interprets the language of claims 1, 5, 11 to include compounds of formula I wherein R3 and R4, together with the carbon atoms they are attached to, form a dioxolane.
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 theinvention, 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 itis most nearly connected, to make and use the same, and shall set forth the best modecontemplated 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 themanner and process of making and using it, in such full, clear, concise, and exact terms as toenable any person skilled in the art to which it pertains, or with which it is most nearlyconnected, to make and use the same, and shall set forth the best mode contemplated by theinventor of carrying out his invention.
Claims 1-3, 5-7, 9-12, 14-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the art that the inventors, at the time the application was filed, had possession of the claimed invention. See MPEP 2163. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filling date of the application, of the specific subject matter claimed by him. Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Claims 1-3, 5-7, 9-10 are drawn to a compound of formula I, or to a composition comprising a compound of formula I, and claims 11-12, 14-20 are drawn to a method of treating cancer with a composition comprising a compound of formula I
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, wherein R3 and R4 are an ethylene oxide, dioxirane, oxetane, dioxetane, dioxolane, dihydrofuran, or furan.
Claims 1-3, 5-7, 9-12, 14-20, taken together with the Specification, embrace hundreds of possible compounds, having combinations of substituents R1, R2 with R3 and R4 substituents such as ethylene oxide
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, dioxirane
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, oxetane
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, dioxetane
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, dioxolane
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, dihydrofuran
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,
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, or furan
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, used to treat cancer.
However, ethylene oxide, dioxirane, dioxetane moieties are known to be unstable and/or highly reactive.
Dembitsky (Oxygen 2024, 4, 181-235, cited in PTO-892) teaches (page 223) that 1,2-dioxetane rings contribute to the molecular diversity seen in natural products, particularly in anti-inflammatory and antiprotozoal therapies. Dembitsky teaches the instability and reactivity of 1,2-dioxetane rings as intermediates in oxidation reactions, with formation of breakdown products. Dembitsky teaches that synthesizing these 1,2-dioxetane ring containing structures in the laboratory remains a significant challenge; the intricate nature of their formation in natural biosynthetic pathways often presents difficulties in replicating these conditions synthetically.
Thus, Dembitsky teaches that there is unpredictability in the field of therapeutic agents containing 1,2-dioxetane rings, given their instability and reactivity.
The level of skill in the art is that of the authors of the references cited to support the examiner’s position (MDs, PhDs, or those with advanced degrees and the requisite experience in drug discovery research).
A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed by him. Applicant has broadly claimed a compound of formula I, a composition comprising a compound of formula I, and a method of treating cancer with a composition comprising a compound of formula I, wherein R3 and R4 are an ethylene oxide, dioxirane, oxetane, dioxetane, dioxolane, dihydrofuran, or furan.
The genus above encompasses hundreds of compounds which comprise at least one ethylene oxide, dioxirane, oxetane, dioxetane, dioxolane, dihydrofuran, or furan functional group. MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 1-3, 5-7, 9-12, 14-20 are broad and generic, with respect to all possible structures encompassed by the instant claims. The claims lack in written description because there is no disclosure of a representative number of species within the very broad claimed genus.
Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus. The specification provides guidance to the synthesis (Figures 1-3) of one compound, namely
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, and its enantiomers (separated by chiral chromatography, Figure 2). This compound does not belong to the genus of formula I (see rejection of claims 4, 8, 13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, above).
Generally, 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 Enzo Biochem, 323 F.3d 956, 966, 63 USPQ2d 1609, 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (Fed. Cir. 1997).
Applicant has disclosed the synthesis of one lignan-“inspired” compound, compositions thereof, and a method of treating breast cancer (Examples 3, 4) or prostate cancer (Example 5)
with said compound or its enantiomers.
The specification does not provide any chemical structure corresponding to a compound of formula I, where R3 and R4 are an ethylene oxide, dioxirane, oxetane, dioxetane, dioxolane, dihydrofuran, or furan.
The specification does not provide sufficient descriptive support for the genus of compounds of formula I claimed. The specification does not provide sufficient descriptive support for practicing the claimed method of treating cancer with the hundreds of compounds embraced by the genus of compounds of formula I.
Considering the state of the art and the high unpredictability in the art, especially given the instability and reactivity of 1,2-dioxetane rings, or that of dioxirane rings, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of claims 1-3, 5-7, 9-12, 14-20.
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:
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (EP 1,527,784, published 4 May 2005, cited in PTO-892), in view of Chen et al. (US 2011/0178171, published 21 July 2011, cited in PTO-892).
Lin (EP 1,527,784) teaches broadly ([0052], page 16, also claim 19) the following compounds of formula I,
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,
wherein
X is, for example, O (page 16, line 22);
A and B are, for example,
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or
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(page 16, line 40, also claim 20),
as antineoplastic compounds, and pharmaceutical compositions thereof, as in instant claim 5, useful to treat cancer [0053], [0066]-[0068], as in instant claim 11.
Lin specifically teaches chaihulactone ([0051], claim 23)
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, where R is methoxy,
which is a compound of formula I
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, where
X = O;
A is
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;
B is
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, and where the compound has a E configuration at a carbon 2(5) position,
as an anti-cancer compound extracted from the Bupleurum scorzonerifolium, effective to treat human hepatoma, ovarian cancer, lung cancer, malignant glioblastoma and colorectal carcinoma [0051], [0067], which is consistent with treating cancer in a human subject, as in instant claim 20.
The composition comprising the compound of the invention is administered intravenously [0068], as in instant claim 16, thus is formulated for intravenous use, as in instant claim 10.
The composition comprising the compound of the invention is administered in combination with anti-cancer drug cisplatin [[0070], as in instant claim 17, as an extract [0069], thus as a pharmaceutical composition comprising a carrier/excipient, as in instant claims 5, 9, 18, 19.
Lin teaches that the compounds of the invention suppress proliferation of Taxol-resistant tumor cell lines [0021], where taxol is mainly used to treat, for example, metastatic breast cancer [0009], which is subtype of cancer of instant claims 14, 15.
Lin does not specifically teach the instant compound
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, nor does he teach a method of treating cancer, such as breast cancer metastatic, with said compound, as in instant claims.
Chen et al. (US 2011/0178171) teach a compound which is
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where R is, for example, H or alkoxy, named compound E-K8, [0007], as racemic mixture, and enantiomers thereof [0039], and pharmaceutical compositions thereof [0015], and a method of treating prostate cancer, as in instant claim 14, including androgen dependent and androgen independent prostate cancer with said compound.
Compound E-Z8 where R is methoxy in Chen is the very compound chaihulactone taught by Lin.
Chen teaches [0037] that the compounds of the invention are effective to treat cancer, such as oral cancer, gastric cancer, colon cancer, breast cancer, as in instant claim 14, prostate cancer, hepatocellular carcinoma, melanoma, lung cancer, glioblastoma, brain tumor, hematopoeitic malignancies, retinoblastoma, renal cell carcinoma, head and neck cancer, cervical cancer, pancreatic cancer, esophageal cancer, and squama cell carcinoma.
Chen teaches ([0133], Table 6, Figure 6) that compound E-K8 above (s.c. administration at 30 mg/kg E-K8) inhibits human xenografts growth in vivo in LNCaP tumor-bearing mice, which is an animal model of prostate cancer, as in instant claim 14.
Chen does not teach the instant compound
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, nor does he teach a method of treating cancer, such as prostate cancer or breast cancer, with said compound, as in instant claims.
It would have been obvious for a person of ordinary skill in the art to combine the teachings of Lin and Chen to arrive at the instant invention.
The person of ordinary skill in the art would have synthesized a compound from the genus of compounds of formula (I) taught by Lin
by replacing the B-substituent
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on the gamma-butyrolactone of formula I
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which is chaihulactone
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R = methoxy,
with another B substituent which is
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because Lin teaches that
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and
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can be used interchangeably as substituents B on a gamma-butyrolactone of formula I. As such, the person of ordinary skill in the art would have replaced a B substituent which is
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with a B substituent which is
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in chaihulactone (also named compound E-Z8 in Chen), with the expectation that the compound retains anti-cancer activity, as taught by Lin and Chen, including anti-cancer activity against prostate cancer or breast cancer, as taught by Chen.
Further, the person of ordinary skill in the art would have explored a positional isomer, namely meta-OH vs. para-OH substituted phenyl ring as B substituent, in such a compound from the genus taught by Lin, with a reasonable expectation that the resulting compound retains anti-cancer activity.
In the absence of unexpected results, stereoisomers are considered obvious variants of each other. "Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties". In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
As such, claims 1-20 are rejected as prima facie obvious.
Conclusion
Claims 1-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S. LUNDGREN can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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