DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of the species ranibizumab in the reply filed on 10 June 2025 is acknowledged.
Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 June 2025.
Status of Application, Amendments, And/Or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The preliminary amendment of 15 September 2022 has been entered in full. Claims 1, 7, 8, and 22-36 are canceled. Claim 18 is withdrawn from consideration as discussed above. Claims 2-6, 9-17, 19-21, 37, and 38 are under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Specifically, the Incorporation by Reference paragraph refers to the size of the file in kilobytes rather than bytes. Upon allowance, the printer will not accept “kilobytes.”
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 incorporation-by-reference paragraph, 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 Objections
Claims 2 and 21 are objected to because of the following informalities: The claims recite the acronyms VEGF, VEGFR2 and VEGFR. In the interest of clarity, acronyms should be spelled out at their first usage, followed by the acronym in parentheses. Subsequent recitations of the term may be by acronym alone. Appropriate correction is required.
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 (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 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.
Claim(s) 2 and 3 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Kwon et al. (US 2014/0315947 A1; published 23 October 2014).
Kwon et al. teach a method of treating Ménière’s Disease (MD) in a subject in need thereof, comprising administering a therapeutically effective dose of a VEGF inhibitor to the subject. See [0032] and [0045]-[0046] regarding treatment of MD. See [0027] and [0032] regarding the VEGF inhibitory activity of at least compounds A1893 and A1938. This anticipates claim 2.
Regarding claim 3, systemic administration is taught at [0050].
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.
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(s) 2-6, 9-17, 19-21, 37, and 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kwon et al. (US 2014/0315947 A1; published 23 October 2014) in view of Ishiyama et al. (March 2017, Scientific Reports 7:253; POI:10.1038/s41598-017-00330-5; pp. 1-10) and Lichter et al. (US 2009/0306225 A1; published 10 December 2009).
Kwon et al. teach a method of treating Ménière’s Disease (MD) in a subject in need thereof, comprising administering a therapeutically effective dose of a VEGF inhibitor to the subject. See [0032] and [0045]-[0046] regarding treatment of MD. See [0027] and [0032] regarding the VEGF inhibitory activity of at least compounds A1893 and A1938.
Kwon et al. do not teach administering a VEGF inhibitor to an affected ear of the subject.
Ishiyama et al. teach that subjects suffering from MD had differential ultrastructural pathological changes in the cellular elements of the microvasculature of the utricular stroma (located in the inner ear), including moderate degeneration of the blood labyrinthine barrier (BLB) and damaged vascular endothelial cells. See abstract. Ishiyama et al. state that understanding the dynamics of the BLB is important to develop therapeutic drug delivery systems to the inner ear to control the BLB inflammatory response (p. 1).
Lichter et al. teach aural formulations to treat diseases of the ear including MD. See abstract; [0033]; [0057]; [0065]; [0099]; [0153]; [0155]-[166]; [0312]. Lichter et al. focus on formulations comprising an active ingredient that can be locally administered to an affected ear of the subject. These formulations can take the form of a hydrogel and/or sustained release formulations, for example. Lichter et al. teach that formulations of this sort can be delivered to the inner ear, including the labyrinth. See [0671]-[0673]. This is relevant to claims 4-6, 11, 12.
Lichter et al. further teach administration of ranibizumab. See [0367]. This is relevant to claims 19-21 and 38. While none of the references explicitly recite at least a 10-fold selectivity of ranibizumab for VEGFR2 over VEGFR, it is noted that this is an inherent feature of ranibizumab, absent evidence to the contrary.
Lichter et al. also teach intratympanic injection of their formulations. See [0034], [0058], for example.
None of the references explicitly teach volumes, w/w amounts, or length of sustained release as recited in claims 9, 10, 13-16, and 37. However, Kwon et al. teach that factors such as dosage are routinely optimized by the ordinary skilled artisan, taking into account such factors as formulating method, manner of administration, age, body weight, sex, morbidity of patient, food, time of administration, route of administration, excretion rate, and response sensitivity. See [0051]. Lichter et al. echo these teachings at [0731], [0816]-[0830], and [0845]-[0846], for examples.
Therefore, it would have been obvious to one of ordinary skill in the art at the time the application was effectively filed to modify the method of treating MD comprising administering a VEGF inhibitor as taught by Kwon et al. by utilizing the localized delivery formulations including extended release, hydrogels, intratympanic injection, and ranibizumab as taught by Lichter et al. with a reasonable expectation of success. The motivation to do so would have been apparent from the teachings of Ishiyama et al. that the microvasculature of the BLB in MD patients is abnormal, and delivery routes effective therefor and effective thereon would be expected to be beneficial.
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 2-6, 9-17, 19-21, 37, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 11-15, 17-22, and 39-45 of copending Application No. 17/797,606 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Both sets of claims recite limitations including treatment of subjects suffering from MD, local administration to the affected ear(s), administration of ranibizumab, overlapping concentrations of effective agents, hydrogels and amounts of gelling agents therein, intratympanic injection, and total amounts of administered formulations.
The claims differ in that the instant claims are limited to treatment of MD whereas the copending claims recite MD in the alternative with other otic diseases/conditions. However, the copending claims clearly suggest treating MD, and render the instant claims obvious in this respect.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH C. KEMMERER whose telephone number is (571)272-0874. The examiner can normally be reached M-F 6:30-3.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ELIZABETH C. KEMMERER/ Primary Examiner, Art Unit 1674
/ECK/
23 June 2025