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 .
Election/Restrictions
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New claims 148-161 are examined together.
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Even though there are three independent claims, according to Applicant, all these claims equivalent to ‘product’ Group I of the original CTRS.
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See below for the species elected.
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.
Claim(s) 148-161 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hobson US20190167804 in view of Pellicciari, J.Med.Chem.1996,39,2874-2876, Kanazawa, Synlett 2019, 30, 1-11, Caputo, Chem. Sci. 2018, 9, 5295, Stepan, J. Med. Chem. 2012, 55, 7, 3414–3424 and US9447026.
Instant elected species Remarks top of numbered page 53
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Hobson at page 12 line 1 teaches
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As seen above the difference is
instant claims replaces
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with
Hobson teaching
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Specifically the difference is the replacement of
benzene
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for bicyclopentane
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moiety
in otherwise identical compound
Hobson does not teach such a replacement.
The teachings, independently of Pellicciari, Kanazawa and Caputo are invoked for the suggestion and motivation for the interchangeable use of
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and
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.
In general, such replacements are generally known in the medicinal chemistry art as ‘Bioisosteric replacement’. Bioisosteric replacement is a core medicinal chemistry strategy in which a functional group or atom within a drug is exchanged for another with similar physical or chemical characteristics. The goal is to retain the drug's target binding and efficacy while improving its pharmacokinetic properties, toxicity profile, or intellectual property position.
Developed by Pellicciari BiCyclo[1.1.1]Pentane BCP
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is a bioisostere for
1,4-disubstituted phenyl ring
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Pellicciari designed the
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replacement as providing the suitable spacer to dispose the pharmacophoric groups in the desired well-defined orientation (see page Figure 2 column A page 2876). Large number of real-life such replacements are known in the in medicinal chemistry art. According to Kanazawa utilization of three-dimensional cyclic scaffolds is important in modern drug discovery, both to provide greater opportunities for optimizing drug candidates and to expand the available chemical space of drugs. Kanazawa that among these scaffolds, bicyclo[1.1.1]pentane (BCP) is a high value bioisostere for 1,4-disubstituted phenyl rings (Abstract). Kanazawa is a Review article that compiles many examples of such replacements in the art, that teaches how and why make such modifications (see Scheme 12) as well modeling information (see Figures 9-1). For example, Kanazawa at top of page 2 column A teaches that an increased three-dimensional character of
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compounds, as measured by Fsp3 (the ratio of the number of sp3-hybridized carbons to the total carbon count) has been found to be associated with a reduced risk of toxicity. See US Patent US9447026 and Stepan titled “Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere” and Caputo throughout for additional examples and for the rationale underpinning for the replacement of
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for
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.
Teachings for the limitations of the dependent claims such as the intermediate (see claim numbered page 10) and the antibodies mAb for the target ADC found throughout Hobson. The following is partial structure in elected species
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. The red line corresponds to the
displacement of the bromo intermediate (claim 152) by mAb. For example, the S in S-A of claim 159 indicates the displacement of bromo by the thiol moiety in antibody fragment.
One of skill in the art would modify the linkers in the conjugates of Hobson with linkers modified as per the teachings of the secondary references with reasonable expectation of success.
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
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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 154, 155, 159, 160 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.
Claims 154, 155, 159, 160 reference Figures in the specification. Patent claims must define the invention independently without relying on the specification or drawings for essential elements, as per MPEP 2173.05(s) Reference to Figures or Tables [R-10.2019].
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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