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 .
Status of the Application
Claims 1-11 are pending in the application. Claims 1-11 are examined herein.
Priority
This application is a DIV of 17/282,378 filed 04/01/2021 PAT 12071430. 17/282,378 is a 371 of PCT/US2019/054583 10/03/2019. PCT/US2019/054583 has PRO 62/742,046 10/05/2018. PCT/US2019/054583 is a CIP of 16/152,008 10/04/2018 PAT 11028078. 16/152,008 is a CIP of 15/162,524 05/23/2016 ABN. 15/162,524 is a CON of 14/343,040 04/10/2014 PAT 9346791. 14/343,040 is a 371 of PCT/US2012/054306 09/07/2012. PCT/US2012/054306 has PRO 61/531,819 09/07/2011.
Applicant’s claim for the benefit of a prior filed application under 35 U.S.C. 119(e) or under or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or earlier-filed nonprovisional application or provisional application for which benefit is claimed). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. 61/531,819, PCT/US2012/054306, 14/343,040, 15/162,524, 16/152,008, PCT/US2012/054306, PRO 62/742,046 fails to provide adequate support and enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The mentioned applications do not disclose a compound of Formula (IV) with the variables D, E, M and N, as currently claimed in instant claim 1. Accordingly, the present application has an effective filing date of 10/03/2019, as the said subject matter is supported by PCT/US2019/054583 filed 10/03/2019.
Information Disclosure Statement
The information disclosure statements submitted on 10/24/2025, 04/07/2025, 09/20/2024, 06/27/2024 (2) are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, there appears to be a clerical error in the structure of Formula (IV) with respect to the positions of the chloro groups in the terminal phenyl attached to the dioxolane ring. The chloro groups should be attached in the ortho and para positions to the point of attachment (as highlighted below), without which none of the compounds of [AltContent: arrow]claim 2 would be encompassed by the Markush structure of Formula (IV).
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Furthermore, in claim 1, some of the functional groups for variable “U” are repeated twice. It is suggested that the duplicates be removed from the claim. For instance,
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is repeated twice.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
The structure of Formula (IV) as noted in the claim objection above should be amended according in the specification.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - 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 1-3, 5 and 7-11 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 a method of treating certain angiogenesis-associated diseases with the compounds of instant Formula (IV), does not reasonably provide enablement for treating “a disease” being broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation” would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
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 re Wands, 8 USPQe2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claims/The nature of the invention
The claims recite a method of treating a disease in a subject, the method comprising administering an effective amount of a compound having structure Formula (IV) (see claim objection above for interpretation of Formula (IV)). The instant specification defines the term “disease” as being generally synonymous, and used interchangeably with the terms "disorder" and "condition" (as in medical condition) and reflects an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning (Para. [0192]). The recitation of the limitation “a disease” is very broad in scope since it encompasses any and every condition known to mankind, given the broadest reasonable interpretation. Therefore, the scope of the conditions being treated by the method claims is extensive.
The state of the prior art/The level of predictability in the art
Vasudev et al. (Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions, 2014, hereinafter Vasudev).
Vasudev teaches that tumors require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands (Abstract). Vasudev teaches one or more of the VEGF ligand family is overexpressed in most solid cancers. However, Vasudev teaches inhibition of VEGF signaling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumors (Abstract; Table 1). Vasudev teaches different types of primary tumors evolve in different organs (e.g. brain, breast, colon, skin, kidney, liver, lung, pancreas, etc.) and the mechanisms with which they evolve in order to vascularize are also different (Pg. 485, second column, fourth full paragraph). Vasudev teaches that predictive biomarkers for this class of agent remains elusive, thereby making it challenging to identify which patients will benefit from these therapies (Pg. 487, first column, first paragraph).
The state of the prior art in the pharmaceutical field involves screening of compounds, both in vitro and in vivo, to help with initial selection or identification of chemical leads with desired pharmacological activities. Further, lead optimization to elucidate the Structure-Activity Relationships (SAR) and Structure Property Relationships (SPR), ultimately lead to selection of compounds as viable efficacious drugs (i.e. identification of compounds that can treat specific disease conditions by a specific mechanism). The development and optimization of useful small molecules is a multi-parameter process. Drug development is a lengthy, complex, and costly process, entrenched with a high degree of uncertainty that a drug will actually succeed. The existence of such obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic use on its face, unquestionably.
Applicants are claiming the compounds of Formula (IV) as effective for treating a “a disease”. In the absence of a showing of correlation between the immense breadth of diseases claimed as capable of treatment by the genus of compounds of claim 1, one of skill in the art is unable to fully predict possible results from the administration of the compounds of the claim. Due to the unpredictability in the field of anti-angiogenic therapy as illustrated above and general unpredictability in the pharmaceutical arts, it is simply impossible to fathom that the recited compounds of the instant invention are capable of treating any and every “type of disease or condition.
The level of one of ordinary skill in the art
The relative level of skill in the art is high, such as, an oncologist or molecular biologist with advanced educational degrees (e.g., M.D. and/or Ph.D.). Additionally there is significant unpredictability in the art regarding the development of therapies, since different diseases have different etiologies.
The amount of direction provided by the inventor/The existence of working examples
The specification does not provide sufficient guidance/protocols for a skilled artisan to practice the claimed method of treating all angiogenesis-associated disease/disorder with any instantly claimed compound of Formula (IV) in its full scope. The instant specification discloses HUVEC inhibition assay for a limited number of compounds (that relates to angiogenesis), wherein only about 4 compounds have the tetrazole moiety (Para. [0265], Table 3). The instant specification discloses the anti-angiogenic activity being validated for a handful of disease conditions (Para. [0272]).
However, the disclosure does not indicate how the disclosed data correlates with the treatment of diseases being claimed broadly. One of ordinary skilled in the art would not be able to practice the method of the instant claims to achieve the intended result of treating any and all diseases.
The quantity of experimentation needed
An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to develop protocols for the claimed vast array of health conditions treated with the compounds of the invention, that have widely different symptoms and etiologies. One of ordinary skill in the art would need to determine what types of health condition, out of the multitude of diseases encompassed by the broad recitation of “a disease” would be benefited by the administration of the compounds of the invention.
Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Considering the state of the art as discussed above, particularly with regards to the high degree of unpredictability in the art with respect to anti-angiogenic therapy 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 scope with the claims.
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 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the claim recites R1, R2, R3 and R4 are each independently selected from the group consisting of hydrogen, trifluoromethyl, … haloalkyl, …, any of which may be optionally substituted”.
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 1 recites the broad recitation haloalkyl the variables R1 to R4, and the claim also recites a narrower recitation of trifluoromethyl for the variables R1 to R4, 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.
Furthermore, the claim recites the closed transitional phrase “consisting of”, which excludes any element, step, or ingredient not specified in the claim. See MPEP 2111.03(II). However, the claim also recites “any of which may be optionally substituted”. This causes some ambiguity regarding the claim scope, since the substituents are not defined in the claim and are extraneous to the elements in the claim, which is not allowed by the “consisting of” phrase.
Therefore, the metes and bounds of claim 1 are indefinite.
For the purpose of applying prior art, claim 1 has been given the broadest reasonable interpretation for the functional groups defining the variables R1 to R4 and without the limitations “the group consisting of”.
Regarding claim 2, the claim recites “or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof”. Para. [0199] of the instant specification defines the term "prodrug" refers to a compound that is made more active in vivo. The instant specification states that prodrugs of the compounds described herein are structurally modified forms of the compound that readily undergo chemical changes under physiological conditions to provide the compound, a wide variety of prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage or oxidative activation of the prodrug. However, the specification does not provide a limiting definition of the term “prodrug. The full scope of the compounds - possible prodrugs encompassed by the claim has not been defined. Therefore the metes and bounds of the claim are indefinite.
For the purpose of applying prior art, claim 2 has been interpreted without the limitation prodrug appearing in the claim.
Claims 3-11 are similarly rejected as depending from a rejected base claim and do not remedy the indefiniteness.
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.
Claim 2 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.
Regarding claim 2, the claim depends from claim 1 and recites “or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof”. However, claim 1 only recites “or an optically pure stereoisomer or pharmaceutically acceptable salt thereof”. This broadens the scope of claim 2, which is improper.
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 § 102
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 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 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.
Claims 1, 3-8 and 10-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beachy et al. (US 2009/0203713 A1, 13 August 2009, hereinafter Beachy).
Regarding instant claim 1, Beachy teaches a method of treating a disorder related to hedgehog pathway activity in a subject comprising administering a compound, with itraconazole being exemplified (Para. [0091]; Claim 6). Itraconazole has the following structure, as evidenced by instant FIG. 1.
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Itraconazole falls within the scope of instant claim 1, wherein
U is
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each of n, m, p and q are 0;
each of A, B, C, D, M, N, X, Y are independently CH.
Regarding instant claims 3-4, Beachy anticipates the method of instant claim 1. Beachy teaches the method can be used to treat cancer (Paras. [0092]-[0093]; Claim 14; Claim 17). Beachy teaches wherein the cancer can be small cell lung cancer, and carcinomas of the esophagus, stomach, pancreas, biliary tract, prostate, and bladder. Other indications appropriate for treatment by this method include basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, ovarian cancer and multiple myeloma (Paras. [0092]-[0093]; Claim 18; Claim 19).
Regarding instant claims 5-6, Beachy anticipates the method of instant claim 1. Beachy teaches hedgehog antagonist compound, especially itraconazole, can be used in the treatment of a disease or disorder or symptoms thereof associated with angiogenesis (Paras. [0131]-[0132]). Beachy teaches embodiments in which the condition associated with hedgehog pathway activity is not cancer (Para. [0016]; Claim 31). Beachy teaches exemplary conditions to include a variety of other keratotic lesions such as actinic keratoses (Para. [0118]) (this reads on the limitation precancerous skin lesions of instant claim 6).
Regarding instant claims 7-8, Beachy anticipates the method of instant claim 1. Beachy teaches pharmaceutical compositions formulated for oral, parenteral, topical, or rectal delivery routes (Para. [0066]). Beachy teaches the pharmaceutical compositions administered as tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, controlled release patch, administration by injection, infusion or inhalation; topical by lotion or ointment (Para. [0066]).
Regarding instant claims 10-11, Beachy anticipates the method of instant claim 1. Beachy teaches combination therapy wherein itraconazole can be co-administered in combination with a chemotherapeutic agent (Para. [0078]).
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 9 is rejected under 35 U.S.C. 103 as being unpatentable over Beachy et al. (US 2009/0203713 A1, 13 August 2009, hereinafter Beachy) as applied to claims 1, 3-8 and 10-11 above, in view of Hussan et al. (A review on recent advances of enteric coating, December 2012, hereinafter Hussan).
The teachings of Beachy are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claim 9, Beachy anticipates the method of instant claim 8. Beachy do not teach wherein the dosage form comprises an enteric coating.
Hussan teaches enteric coated tablets are solid unit dosage forms which are designed to bypass the stomach and release the drug in small intestine (Abstract). Hussan teaches suitable materials for enteric coatings include CAP, CAT, PVAP and HPMCP, fatty acids, waxes, shellac, plastics and plant fibers (Abstract; Pg. 7, Table no. 1). Hussan teaches various advantages of enteric coated formulations to include protection of active ingredients from the acidic environment of the stomach, minimizing first pass metabolism of drugs, to provide a delayed-release component for repeat action, to prevent gastric distress or nausea from a drug due to irritation (Pg. 6, sixth full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Beachy and Hussan to have formulated an enterically coated itraconazole to arrive at the method of instant claim 9 with a reasonable expectation of success. The motivation being to provide the added advantage of protecting the active ingredient from the acidic environment of the stomach, minimizing first pass metabolism, providing a delayed-release component for repeat action, preventing gastric distress or nausea from a drug due to irritation (Hussan, Pg. 6, sixth full paragraph).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Note to Applicant: Although the instant application is a divisional application of the parent application 17/282,378 now patent 12,071,430 B2, the prohibition against nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply due to the following reasons:
the claims of the application under examination and issued patent are not consonant with the restriction requirement made by the examiner in the Office action dated 05/31/2023
the restriction requirement set forth in the Office action dated 05/31/2023 was withdrawn in the Office action dated 03/18/2024. With the withdrawal of the restriction requirement, the non-elected claims that are no longer withdrawn from consideration become subject to examination. "The restriction requirement disappears; it is as though it had not been made. With the disappearance of the restriction requirement, the need for a divisional application and the need for the [double patenting] prohibition also disappear." In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 132 (CCPA 1971). See MPEP 804.01 for more information.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,071,430 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn itraconazole analogs.
The instant claims are drawn to a method of treating a disease in a subject, the method comprising administering an effective amount of a compound having structure Formula (IV) (see claim objection above for interpretation of Formula (IV)).
The claims of the reference ‘430 patent are drawn to a method of treating a disease in a subject, the method comprising administering an effective amount of the compound according to claim 1 of the reference patent.
Claim 2 of the reference ‘430 patent anticipates the compounds of instant claim 2. Claims 4-5 of the reference ‘430 patent anticipates instant method claims 3-4. Claims 6-7 of the reference ‘430 patent anticipates instant method claims 5-6. Claims 8-10 of the reference ‘430 patent anticipates instant method claims 7-9. Claims 11-12 of the reference ‘430 patent anticipates instant method claims 10-11.
Thus, claims 1-12 of U.S. Patent No. 12,071,430 B2 and instant claims 1-11 are not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 12,545,666 B2 in view Beachy et al. (US 2009/0203713 A1, 13 August 2009, hereinafter Beachy) and Hussan et al. (A review on recent advances of enteric coating, December 2012, hereinafter Hussan).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn a method of treating a disease in a subject comprising administering an effective amount an itraconazole analog.
The instant claims are drawn to a method of treating a disease in a subject, the method comprising administering an effective amount of a compound having structure Formula (IV) (see claim objection above for interpretation of Formula (IV)).
The claims of the reference ‘666 patent are drawn to a method of treating cancer in a subject in need thereof, comprising administering an effective amount of a compound according to claim 1 of the reference patent.
The method of claim 1 of the reference ‘666 patent anticipates the method of instant claims 1-2. Claim 2 of the reference ‘666 patent anticipates instant method claims 3-4. The claims of the reference ‘666 patent do not teach the limitations of instant claims 5-11.
Beachy teaches a method of treating a disorder related to hedgehog pathway activity in a subject comprising administering a compound, with itraconazole being exemplified (Para. [0091]; Claim 6). Beachy teaches hedgehog antagonist compound, especially itraconazole, can be used in the treatment of a disease or disorder or symptoms thereof associated with angiogenesis (Paras. [0131]-[0132]). Beachy teaches treating keratotic lesions such as actinic keratoses (Para. [0118]) (this reads on the limitation precancerous skin lesions of instant claim 6). Beachy teaches pharmaceutical compositions formulated for oral, parenteral, topical, or rectal delivery routes (Para. [0066]). Beachy teaches the pharmaceutical compositions administered as tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, controlled release patch, administration by injection, infusion or inhalation; topical by lotion or ointment (Para. [0066]). Beachy teaches combination therapy wherein itraconazole can be co-administered in combination with a chemotherapeutic agent (Para. [0078]).
Hussan teaches enteric coated tablets are solid unit dosage forms which are designed to bypass the stomach and release the drug in small intestine (Abstract). Hussan teaches suitable materials for enteric coatings include CAP, CAT, PVAP and HPMCP, fatty acids, waxes, shellac, plastics and plant fibers (Abstract; Pg. 7, Table no. 1). Hussan teaches various advantages of enteric coated formulations to include protection of active ingredients from the acidic environment of the stomach, minimizing first pass metabolism of drugs, to provide a delayed-release component for repeat action, to prevent gastric distress or nausea from a drug due to irritation (Pg. 6, sixth full paragraph).
Therefore, given the teachings of Beachy and Hussan, it would have been prima facie obvious to one of ordinary skill in the art to have utilized the compounds of the reference ‘078 patent in a method of treating a disease or condition associated with angiogenesis, to arrive at the method of the instant claims with a reasonable expectation of success. Beachy teaches conditions besides cancer, such as actinic keratoses respond to modulation of such Hedgehog pathways/angiogenesis by itraconazole. This renders the method of treatment as in instant claims 5-6 prima facie obvious. Beachy teaches formulations that render the formulations of instant claims 7-9 prima facie obvious in view of Hussan. Beachy teaches a combination therapy that renders the method of instant claims 10-11 prima facie obvious.
Thus, claims 1-2 of U.S. Patent No. 12,545,666 B2 and instant claims 1-11 are not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,028,078 B2 in view Beachy et al. (US 2009/0203713 A1, 13 August 2009, hereinafter Beachy) and Hussan et al. (A review on recent advances of enteric coating, December 2012, hereinafter Hussan).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn itraconazole analogs.
The instant claims are drawn to a method of treating a disease in a subject, the method comprising administering an effective amount of a compound having structure Formula (IV) (see claim objection above for interpretation of Formula (IV)).
The claims of the reference ‘078 patent are drawn to compounds and a pharmaceutical composition thereof. The claims of the reference ‘078 patent teaches a species of compound shown below.
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Compound 214 of the reference ‘078 patent anticipates compound 14 of instant claim 2, and compound of Formula (IV) of instant claim 1 wherein,
U is
PNG
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49
100
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;
each of n, m, p and q are 0;
each of A, C, D, M, N, X, Y are independently CH;
B is N.
Looking into the disclosure of the reference ‘078 patent for utility of the compounds, the patent teaches the itraconazole analog compounds as involved in the inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 ( VEGFR2 )
glycosylation, angiogenesis (Abstract; Col. 12, Lns. 37-43; Table 3).
The reference ‘078 patent do not teach a method of treating a disease in a subject comprising administering an effective amount of a compound having structure Formula (IV).
Beachy teaches a method of treating a disorder related to hedgehog pathway activity in a subject comprising administering a compound, with itraconazole being exemplified (Para. [0091]; Claim 6). Beachy teaches the method can be used to treat cancer (Paras. [0092]-[0093]; Claim 14; Claim 17). Beachy teaches wherein the cancer can be small cell lung cancer, and carcinomas of the esophagus, stomach, pancreas, biliary tract, prostate, and bladder. Other indications appropriate for treatment by this method include basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, ovarian cancer and multiple myeloma (Paras. [0092]-[0093]; Claim 18; Claim 19). Beachy teaches hedgehog antagonist compound, especially itraconazole, can be used in the treatment of a disease or disorder or symptoms thereof associated with angiogenesis (Paras. [0131]-[0132]). Beachy teaches treating keratotic lesions such as actinic keratoses (Para. [0118]) (this reads on the limitation precancerous skin lesions of instant claim 6). Beachy teaches pharmaceutical compositions formulated for oral, parenteral, topical, or rectal delivery routes (Para. [0066]). Beachy teaches the pharmaceutical compositions administered as tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, controlled release patch, administration by injection, infusion or inhalation; topical by lotion or ointment (Para. [0066]). Beachy teaches combination therapy wherein itraconazole can be co-administered in combination with a chemotherapeutic agent (Para. [0078]).
Hussan teaches enteric coated tablets are solid unit dosage forms which are designed to bypass the stomach and release the drug in small intestine (Abstract). Hussan teaches suitable materials for enteric coatings include CAP, CAT, PVAP and HPMCP, fatty acids, waxes, shellac, plastics and plant fibers (Abstract; Pg. 7, Table no. 1). Hussan teaches various advantages of enteric coated formulations to include protection of active ingredients from the acidic environment of the stomach, minimizing first pass metabolism of drugs, to provide a delayed-release component for repeat action, to prevent gastric distress or nausea from a drug due to irritation (Pg. 6, sixth full paragraph).
Therefore, given the teachings of Beachy and Hussan, it would have been prima facie obvious to one of ordinary skill in the art to have utilized the compounds of the reference ‘078 patent in a method of treating a disease or condition associated with modulation of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis, to arrive at the method of the instant claims with a reasonable expectation of success. Beachy teaches conditions, such as cancer and actinic keratoses respond to modulation of such pathways by itraconazole. Beachy teaches formulations that render the formulations of instant claims 7-9 prima facie obvious in view of Hussan. Beachy teaches a combination therapy that renders the method of instant claims 10-11 prima facie obvious.
Thus, claims 1-2 of U.S. Patent No. 11,028,078 B2 and instant claims 1-11 are not patentably distinct.
This is a nonstatutory double patenting rejection.
Conclusion
Claims 1-11 are rejected.
Claim 1 is objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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