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
The preliminary amendment filed on 9/25/2024 is acknowledged. Claims 1-8 and 12-20 are currently pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements filed on 4/03/2026 and 5/01/2026 are acknowledged and have been considered except where lined through.
Drawings
The drawings are objected to for being in a foreign language. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 - 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).
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 Objections
Claims 1-4, 15 and 19 are objected to because of the following informalities:
It is suggested that Applicants amend the claims to replace the phrase “In the chemical Formula Ia” to “wherein”. Additionally, it would be helpful to subscript the numbers. For example, C1-6 alkyl vs. C1-6alkyl, as currently claimed. 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.
Claim(s) 1-6 and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bioland (WO2012102560A2, 2012-08-02 cited in the IDS as KR20120086538) English translation provided by Google Patents.
Bioland teach methylhonokiol derivatives and compositions comprising said derivatives for the treatment of inflammatory diseases, wherein the compounds inhibit COX-2 activity (abstract). With regards to the derivatives, Bioland teaches intermediates having the structures:
PNG
media_image1.png
115
128
media_image1.png
Greyscale
,
PNG
media_image2.png
80
103
media_image2.png
Greyscale
and
PNG
media_image3.png
78
105
media_image3.png
Greyscale
which read on compounds 1, 7 and 44 of claims 5 and 6, as well as, compounds having the structures:
PNG
media_image4.png
97
98
media_image4.png
Greyscale
PNG
media_image5.png
128
424
media_image5.png
Greyscale
which read on compounds 2, 12, 16 and 20 of claim 5 (see Example 22, preparation of derivative 23 and Table 22). With regards to the inflammatory diseases, Bioland teaches that inflammatory disease that can be treated included, but are not limited to, macular degeneration (paragraph starting with “According to a preferred embodiment”.
Claim(s) 1-6 and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yuan et al. (Bioorganic & Medicinal Chemistry Letters 2019; 29: 329-333, IDS).
Yuan et al. teach the synthesis and anti-neuroinflammatory activity of N-heterocyclic analogs based on the natural biphenyl-neolignan honokiol (Title). With regards to the analogs, Yuan et al. teach analogs having the following structure:
PNG
media_image6.png
76
193
media_image6.png
Greyscale
PNG
media_image7.png
27
55
media_image7.png
Greyscale
and
PNG
media_image8.png
556
335
media_image8.png
Greyscale
which reads on numerous compounds of claims 5 and 6 including, but not limited to, compounds 21-25 (page 330, Figure 2 and Scheme 1 and page 331, Table 1). Moreover, Yuan et al. teach IC50 values and cell viability in vitro data of the compounds (Table 1).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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) 12-13, 15-17 and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bioland (WO2012102560A2, 2012-08-02 cited in the IDS as KR20120086538) English translation provided by Google Patents, as applied to claims 1-6 and 8, in view of Zhang et al. (PLoS ONE 2016; 11(1): e0146808) as evidenced by Durhuus (Sci Rep 11, 8226 (2021). doi.org/10.1038/s41598-021-87337-1).
Bioland teach methylhonokiol derivatives and compositions comprising said derivatives for the treatment of inflammatory diseases, wherein the compounds inhibit COX-2 activity (abstract). With regards to the derivatives, Bioland teaches intermediates having the structures:
PNG
media_image1.png
115
128
media_image1.png
Greyscale
,
PNG
media_image2.png
80
103
media_image2.png
Greyscale
and
PNG
media_image3.png
78
105
media_image3.png
Greyscale
which read on compounds 1, 7 and 44 of claims 5 and 6, as well as, compounds having the structures:
PNG
media_image4.png
97
98
media_image4.png
Greyscale
PNG
media_image5.png
128
424
media_image5.png
Greyscale
which read on compounds 2, 12, 16 and 20 of claim 5 (see Example 22, preparation of derivative 23 and Table 22). With regards to the inflammatory diseases, Bioland teaches that inflammatory disease that can be treated included, but are not limited to, macular degeneration (paragraph starting with “According to a preferred embodiment”.
Bioland does not specifically select macular degeneration as the inflammatory condition.
Zhang et al. teach that choroidal neovascularization (CNV) is an important pathological component of neovascular age-related macular degeneration (AMD), wherein administration of a COX-2 antagonist attenuated experimentally induced CNV lesions and subretinal fibrosis (abstract). In conclusion, Zhang et al. teach that the results provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis (conclusion). While the prior art does not specifically teach that AMD is associated with accumulation of A2E in the eyes, as evidenced by Durhuus, accumulation of drusen and lipofuscin in RPE cells constitutes the hallmark of AMD, wherein the main components of lipofuscin are fluorescent bisretinoids, such as A2E (page 2, 2nd full paragraph). As such, the claimed limitation appears to be met.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Bioland to specifically treat macular degeneration in view of the teachings of Zhang et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Bioland teaches that the derivatives are useful for treating a variety of inflammatory conditions including macular degeneration through the inhibition of COX-2; and
-Zang et al. provide a proof of concept that OCX-2 inhibition in treating subretinal fibrosis which is associated with age relate macular degeneration.
As such, an ordinary skilled artisan would have been motivated to make such a modification to predictably treat macular degeneration.
Conclusion
Therefore, Claims 1-6, 8, 12-13, 15-17 and 19-20 are rejected.
Claims 7, 14 and 18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 7, the closest prior art to claim 7 is considered to be Yuan et al. (Bioorganic & Medicinal Chemistry Letters 2019; 29: 329-333, IDS) described above and incorporated herein. While Yuan et al. teach piperazine derivatives, there is no teaching or suggestion to specifically select these compounds for modification (see page 332, 2nd column, 1st paragraph). Regarding claims 14 and 18, the state of the art at the time of filing recognize that there are certain morphologic features to further characterize AMD based on the presence or absence of choroidal neovascularization (CNV), wherein “dry” is nonexudative or nonneovascular and “wet” is exudative or neovascular (see Thomas et al. (Med. Clin. N. Am. 2021; 105: 473-491, specifically page 476). Thus, there is no reasonable expectation that a COX-2 inhibitor can successfully treat “dry” age related macular degeneration which is absent in choroidal neovascularization.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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, 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.
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.
BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
Prosecution Insights