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 .
Application Status
Claims 1-12 are pending and examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because there are peptide sequences over 4 amino acids long in the instant specification in Table 3 without sequence identifiers.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See Table 3, page 15.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Interpretation
Claims 1 and 12 are drawn to an HIF-1α modulator. A “HIF-1α modulator” is being interpreted as anything that inhibits, activates, changes the expression level, or post translationally modifies HIF-1α.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10 and 11 recite the limitation "the kit of claim 9" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 9 is drawn to a method not a kit. This rejection can be obviated by amending claims 10 and 11 to “the method of claim 9.” For the purpose of compact prosecution claims 10 and 11 will be examined as reciting “the method of claim 9.”
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 1-7, 9, and 11-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harter (US 2014/0329797 A1; PTO-892).
Regarding claims 1, 4, and 12, Harter teaches substituted oxadiazolyl pyridinones and oxadiazolyl pyridazinones as HIF inhibitors (title), a compound of formula (I) (claim 1) and a pharmaceutical composition comprising a compound as defined in claim 1 in combination with one or more inert nontoxic pharmaceutically suitable excipients (claim 11).
Regarding claim 12, Further printed instructions do not distinguish the claimed product (MPEP 2112.01 (III)).
Regarding claims 2-3, Harter teaches oral and parenteral administration are preferred, especially oral and intravenous administration and that the compounds according to the invention can be converted to the administration forms mentioned which can be done in a manner known per se, by mixing with inert, nontoxic, pharmaceutically suitable excipients, which can include carriers (for example microcrystalline cellulose, lactose, mannitol), solvents (e.g. liquid polyethylene glycols), emulsifiers and dispersing or wetting agents (for example sodium dodecylsulphate, polyoxysorbitan oleate), binders (for example polyvinylpyrrolidone), synthetic and natural polymers (for example albumin), stabilizers (e.g. antioxidants, for example ascorbic acid), dyes (e.g. inorganic pigments, for example iron oxides) and flavour and/or odour correctants (paras 0305-6); this reads on liquid and solid state compositions.
Regarding claims 5-6, Harter teaches the object of the present invention was therefore to provide novel compounds which act as potent inhibitors of the transactivating action of the transcription factor HIF and can be employed as such for treatment and/or prevention of disorders, in particular of hyperproliferative and angiogenic disorders, such as cancer and tumour disorders (para 0010).
Regarding claim 7, Harter teaches a method for the treatment of cancers or tumours comprising administering to a human or mammal in need thereof a therapeutically effective amount of a compound from claim 1 (claim 9).
Regarding claims 9 and 11, Harter teaches a method for the treatment and/or prevention of ischaemic cardiovascular diseases, heart failure, myocardial infarction, arrhythmia, stroke, pulmonary hypertension, fibrotic diseases of the kidney and lung, psoriasis, diabetic retinopathy, macular degeneration, rheumatic arthritis or Chuvash polycythaemia (claim 10).
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.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Harter (US 2014/0329797 A1; PTO-892) as applied to claims 1-7, 9, and 11-12 above, and further in view of Druzgala (WO 2015/131231 A1; PTO-892).
The teachings of Harter regarding claims 1-7, 9, and 11-12 are detailed above.
Harter does not teach that the cancer is kidney renal clear cell carcinoma.
Druzgala teaches that Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant genetic condition that predisposes individuals to benign and malignant tumors including clear cell renal cell carcinomas (ccRCC) (para 00333). Druzgala further teaches that VHL regulates HIF1α by binding to it in the presence of oxygen to cause its degradation in the proteasome (para 00333). Drugzala further teaches that the lifetime risk of developing ccRCC in VHL disease patients is more than 70% by the age of 60 years and that the kidneys of VHL disease patients display cystic changes or distortion of the tubular structure adjacent to cells that express HIF1 and cells in these early lesions overexpress HIF1 a target genes (para 00334). Drugzala further teaches a method of preventing, treating or reversing a disease with an effective amount of perhexiline wherein the disease is associated with, caused by, or results in hypoxia (abstract). Drugzala further provides example 17 that demonstrates perhexiline can treat ccRCC (para 00335).
It would be obvious to one of ordinary skill in the art before the effective filing date of the instant application to apply a modulator of HIF1α as taught by Harter to renal ccRCC as taught by Drugzala. The ordinary artisan would be motivated to do so because Drugzala teaches VHL is directly involved in regulating HIF1α and that people with VHL disease have a high risk of developing ccRCC that is associated with overexpression of HIF1α target genes. The ordinary artisan has a reasonable expectation of success as Harter and Drugzala are analogous arts that modulate the activity of HIF1α to treat various disease associated with hypoxia.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Harter (US 2014/0329797 A1; PTO-892) as applied to claims 1-7, 9, and 11-12 above, and further in view of Rabinowitz (US 10,975,062 B2; PTO-892).
The teachings of Harter regarding claims 1-7, 9, and 11-12 are detailed above.
Harter does not teach treatment of gastrointestinal ulcers.
Rabinowitz teaches that prolyl hydroxylase (PHD) and HIF play a central role in tissue repair and regeneration including healing of wounds and ulcers (col 7, lines 4-5). Rabinowitz further teaches that PHD enzymes mediate the cell response to hypoxia via post translational modification of HIF, in that inhibition of PHD blocks degradation of HIF (col 2, lines 48-64). Rabinowitz further teaches that inhibition of PHD is expected benefit healing of gastrointestinal ulcers (col 7, lines 58-61).
It would be obvious to one of ordinary skill in the art before the effective filing date of the instant application to apply a modulator of HIF1α as taught by Harter to gastrointestinal ulcers as taught by Rabinowitz. The ordinary artisan would be motivated to do so because Rabinowitz also teaches a modulator of HIF1α that increase expression be decreasing degradation and would provide a benefit to the healing of gastrointestinal ulcers. The ordinary artisan has a reasonable expectation of success as Harter and Rabinowitz are analogous arts that modulate the activity of HIF1α to treat various disease associated with hypoxic conditions.
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, 4, 5-7, and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No.10,729,692 B2, as evidenced by Zhao (bioRxiv preprint, this version posted October 20, 2020; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1, 4, 5-7, and 12, the patented claims teach a pharmaceutical composition comprising: a cyclin dependent kinase inhibitor (CDKI) including palbociclib or abemaciclib and a heat shock protein 90 (HSP90) inhibitor (claims 1-2).
As evidenced by Zhao, HIF1α inhibition by dual targeting of CDK4/6 and HSP90 reduces cancer cell viability including Rb-deficient cells (title). Zhao further teaches that palbociclib is CDK 4 inhibitor and abemaciclib is an CDK 4/6 inhibitor (page 7, para 3 and page 8, para 2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643