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 Claims and Response to Restriction Requirement
Claims 1-24 are pending as of the response filed 09/02/2025 in response to the Office action dated 07/02/2025 in this transfer case. Applicant’s election of a species of E3 ligase binding moiety (EBM) without traverse as shown below, wherein G is -C(=O) and Ring A is not substituted with one or more F atoms, is acknowledged.
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Applicant’s election without traverse of a species of disease to be treated as breast cancer, is acknowledged. Claims 1-24 encompass the elected species. Claims 1-24 are examined herein.
The compounds of formula (I) as in instant claim 1 characterized by a TMPBM of formula (II) has been found to be free of prior art (see claim interpretation below regarding the limitation “prodrug”). In view of the pending claims, the following objections/rejections are made, as discussed below.
Priority
This application is a 371 of PCT/EP2020/079281 filed 10/16/2020, and claims foreign priority to EP 19203700.0 filed 10/16/2019.
Information Disclosure Statement
The information disclosure statements submitted on 11/13/2023 and 11/08/2024 have been considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 28, second paragraph – third paragraph of the instant specification (there are six embedded hyperlinks listed). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), 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 EFS-Web or Patent Center 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 EFS-Web or Patent Center 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:
Missing or Defective Incorporation by Reference Paragraph
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.
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 1, 11-13 are objected to because of the following informalities:
In claim 1, for consistency of notations it is suggested that the definition of R1-R8 groups be amended to read “R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from -H, -halogen, -NO2, -CN, -C1-3 alkyl, -OH, -O-C1-2 alkyl, -NH2, -NH(C1-2 alkyl), -N(C1-2 alkyl)2, -CHO, -CO(C1-2 alkyl), -COOH, -COO(C1-2 alkyl), -CONH2, -CONH(C1.2 alkyl), and -CON(-C1-2 alkyl)2”, by including the point of attachment to each of the functional groups.
Claim 11-13 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only--, and/or, --cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 11-13 have not been further treated on the merits.
Appropriate correction is required.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Fig.9 and Fig. 10 reference d9A-2, however, page 70 of the instant specification mentions “d9A1-2”. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) 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. 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.
Claim Rejections - 35 USC § 112 - Written Description
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 1-10 and 14-24 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 claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding instant claims 1 and 23-24, the claim recites a compound having formula (I), with the moieties as defined and method of use thereof.
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While claim 1 recites the TMPBM having formula (II), the linker group and EBM moiety are broadly claimed and can have highly divergent structures. Furthermore, claims 23-24 recite “a method of use in treating a disease comprising administering a therapeutically effective amount of the compound of claim 1 to a subject in need of such a treatment”. Page 34, second paragraph of the instant specification defines “a disease” as “any condition that would benefit from treatment with a composition described herein”. Page 34 last paragraph to page 50 continued paragraph list conditions ranging from neurodegenerative diseases, such as, dementia, Alzheimer’s, ADHD; to anemias; to childhood tic disorders; to neoplasms; to congestive heart failure; to constipation; to liver failure; to viral infections, etc.. The genus of TMPBM-L-EBM compounds claimed encompass a highly divergent variety of core structures, which includes species that do not share both a substantial structural feature and a common function that flows from the substantial feature. The different moieties would be presumed by one of ordinary skill in the art to have different physical properties (e.g. solubility, stability, etc.) that would lead to different biological activities (e.g. ADME and PK/PD, efficacy, toxicity, etc.). In addition, each of these compounds, as claimed, can be a pharmaceutically acceptable salt, solvate or prodrug. However, the specification does not provide a reasonably representative disclosure of the TMPBM-L-EBM compounds overall. Specifically, the specification discloses a limited number of species of the TMPBM-L-EBM compound directed to compounds CP-19076070-1 to CP-19076070-4 representing the TMPBM group of structure (II) (instant specification, page 72) and the synthesis of the same (instant specification, pages 73-87). The specification discloses a small number of the bifunctional compounds as depicted in Fig. 8 (4 compounds) versus the breadth of compounds claimed. As such, any condition appears to fall within the scope of the method claims. And, the compound of claim 1, drawn to a broad genus is claimed to treat any such condition. There is no disclosure regarding how all types of conditions claimed to be treated, having diverse etiologies can be treated using the compounds of claim 1 (drawn to a broad genus of compounds).
These are not viewed as being reasonably representative of the genus in its claimed scope because no readily apparent combination of identifying characteristics is provided, other than the disclosure of those specific species as examples of the claimed genus, wherein the TMPBM-L-EBM compounds can be used in the treatment of various unrelated diseases. It is not readily apparent that the genus of compounds claimed have a structural entity in common, that leads to property of these compounds to be used in the treatment of a divergent vast array of conditions claimed to be treated.
According to MPEP 2163 (II) (3) (a) (ii), The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification’)”).
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed … Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces … If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph.
In the instant case, Applicants have claimed a large genus of compounds as being configured to treat any and every known disease. However, there is no guidance as to the necessary features of the compounds, say physical, chemical or structural, that lead to this property. Therefore, there is no evidence Applicants had possession of the full genus of compounds at the time of filing, because the specification does not conclusively demonstrate the structure-activity relationship of the claimed vast array of compounds, towards their use in a method of treatment of any and every disease. Thus, the written description requirement for the claimed genus of compounds towards the method of treating a disease in a subject in need thereof, has not been met.
Claims 2-10 and 14-22 depend directly or indirectly from claim 1 and are similarly rejected.
In response to this rejection, the Applicant can amend the claim(s) to recite only individual species or grouping of species that share a substantial structure as well as a common function that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a common function that flows from the substantial structural feature for it to be capable of being used in the treatment of any disease.
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 1-10 and 14-24 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 instant claim 1, the claim recites “wherein TMPBM is a moiety having the following partial formula (II) …”. The recitation of the limitation “partial” renders the scope of the claim indefinite. It is unclear if the TMPBM moiety includes additional functional groups besides that of formula (II). This renders the metes and bounds of the claim indefinite.
Claims 2-4 also recite the term “partial” and are similarly rejected.
Claims 5-10 and 14-24 either directly or indirectly depend from claim 1 and are similarly rejected.
For the purpose of applying prior art, all claims have been interpreted to read without the occurrence of the limitation “partial” appearing in the claims.
Additionally, regarding instant claim 1, the claim recites wherein TMPBM is a moiety having the following partial formula (II) or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug”. A prodrug generally represents derivatives that are converted to the compound of the present invention by reacting with enzymes, gastric acids, and the like under physiological conditions in vivo. In other words, a prodrug is any compound which is pharmaceutically active in vivo when it undergoes metabolic degradation. The instant specification does not provide any disclosure of what these compounds might be that transform in vivo into the instantly claimed compounds. Since 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 is indefinite.
Claims 2-10 and 14-24 either directly or indirectly depend from claim 1 and are similarly rejected.
For the purpose of applying prior art, claim 1 has been interpreted to read without the occurrence of the limitation “prodrug” appearing in the claim.
Allowable Subject Matter
The compounds of formula (I) as in instant claim 1 characterized by a TMPBM of formula (II) has been found to be free of prior art.
Conclusion
Claims 1-10 and 14-24 are rejected.
Claims 1, 11-13 are objected to.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PADMAJA S RAO whose telephone number is (571)272-9918. The examiner can normally be reached 9:00-5:30 pm EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.S.R./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627