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 .
Information Disclosure Statement
The information disclosure statement (IDS), dated 09/09/2025, comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 09/09/2025 are acknowledged.
In light of claim amendments, previous 112(b) rejection is withdrawn.
However, applicants’ arguments for the previous 112(a) written description rejection are found not persuasive. Accordingly, the previous rejection is maintained. Please see the examiners response to applicants below.
Response to Arguments
Applicants’ main argument is that claims are amended to recite particular linkers as exemplified in the present application, and the presently claimed compounds share the common activity of apoptosis protein inhibition activity and common chemical structure for the claimed formula I.
At least in claim 1, all are variables, and there is not core structure to represent claimed formula I. For example, based on the definition of X, the fused rings can produce three types of divergent heterocyclic rings and the properties of these compound are expected to be different. The variables, R1-R5, on the structure ranges from simple H to complex heterocyclic rings. Properties with Hs are obviously expected to be different from that of heterocyclic rings. Further, stereoisomer means, the claimed compound can be in all possible isomers, other than constitutional (structural) isomers.
With regard to linkers, it appears that there is no defined core structure for the linker. Moreover, linker can be defined with a simple bond or a complex heterocyclic rings.
Shown data and its function is limited to the species X=C and O, and limited number of linkers. No data is shown for X is N. The recited binding properties in Table 5 ranges from 1 nM to >1 microM. So, the provided data is very limited.
Based on the above reasoning, in absence of data for the broadly claimed variables, there is no common chemical structure for formula I and so, properties are expected to be different, absent evidence to the contrary.
Claim Rejections - 35 USC § 112 – Written Description [Maintained]
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 1-18, 20 and 26 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 for the claimed method. 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The rejection is based on the requirement(s), i.e., the guidelines provided by the MPEP 2163.04. These are listed below:
(A) identify the claim(s) limitations at issue, and
(B) establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed. The MPEP 2163 further provided or expanded the guidelines for the written description requirements.
(A) IDENTIFY THE CLAIM LIMITATIONS AT ISSUE:
Independent claim 1 is drawn to the compound of formula I, a stereoisomer thereof. Variables in formula I are defined by recited specific species and sub-genus to genus.
In the claim 1, all are variables. It appears that linker is defined with all possible chemical groups broadly. Stereoisomer means, the claimed compound can be in all possible isomers, other than constitutional (structural) isomers. Based on the definition of X, the fused rings can produce three types of divergent heterocyclic rings and the properties of these compound are expected to be different. The variables, R1-R5, on the structure ranges from simple H to complex heterocyclic rings.
Dependent claims are limited to the recited species for variables of formula I. Claims 2-12 define structural features of linker and it appears that there is no define core structure for the linker. Moreover, linker can be defined with simple bond to complex heterocyclic rings.
The claimed compound is associated with a specific property. How these divergent variables and divergent linkers affect the end property of the claimed compound.
So, the issue is in the scope of the broadly recited variables in the formula I, in other words there is no established core structure for the formula I. Applicants specification is also failed to describe the core structure, which is responsible for its activity, in other words, the structure/function relationship for the claimed generic formula I is not described. In its absence of clear definition makes the invention unpredictable, and cannot be understood by a skilled person in the art.
Applicants can claim as broadly as possible for the claimed invention. However, if there is a variability in the genus or broadly claimed subject matter, and if the variability expects unpredictability or uncertainties for the claimed subject matter, then specification must describe the possible uncertainties in the broadly claimed genus, so that a skilled person in the art can understands the invention and can reproduce applicants claimed invention. In its absence, it makes the invention unpredictable, and cannot be envisioned by a skilled person in the art.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure. See MPEP 2163 II(A)(3)(a)(ii).
The number of species that describe the genus must be adequate to describe the entire genus. However, if there is substantial variability, a large number of species must be described.
The formula I can generate thousands of divergent compounds, based on at least X and linkers, and the question is (i) did applicants provide enough description for making possible X and linkers with all possible variables? (ii) will all the generated compounds be capable of retain its property? Based on (i) and/or (ii), will a skilled person in the art understand the claimed invention?
(B) ESTABLISH A PRIMA FACIE CASE BY PROVIDING REASONS WHY A PERSON SKILLED IN THE ART AT THE TIME THE APPLICATION WAS FILED WOULD NOT HAVE RECOGNIZED THAT THE INVENTOR WAS IN POSSESSION OF THE INVENTION AS CLAIMED IN VIEW OF THE DISCLOSURE OF THE APPLICATION AS FILED:
The further analysis for adequate written description considers, see MPEP 2163, the following:
(A) Determine whether the application describes an actual reduction to practice of the claimed invention:
Not provided. The claimed genus of formula I can generate thousands of compounds. Shown data and its function is limited to the species X=C and O, limited number of linkers. No data is shown for X is N. The recited binding properties in Table 5 ranges from 1 nM to >1 microM. So, the provided data is very limited.
Accordingly, applicants failed to describe actual reduction to practice of the claimed invention.
(B) If the application does not describe an actual reduction to practice, determine whether the invention is complete as evidenced by a reduction to drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole:
No drawings are provided in the specification.
(C) If the application does not describe an actual reduction to practice or reduction to drawings or structural chemical formula as discussed above, determine whether the invention has been set forth in terms of distinguishing identifying characteristics, such as structure/function correlations, as evidenced by other descriptions of the invention that are sufficiently detailed to show that applicant was in possession of the claimed invention:
Heterocyclic rings with different heteroatoms show divergent properties. In this case, the properties of hetero ring, where X is O or N is expected to different from that of ring comprising C for X. Even O and N containing hetero rings show different properties. Art also established the fact that the properties of conjugates, in this case formula I and its properties, are sensitive to the linker moiety [see section 6 in He et al, Molecules, 2019, 24, 1855, 1-34; see abstract and conclusion in Lu et al, International Journal of Molecular Sciences, 2016, 17, 561, 1-22].
The art also recognizes that the choice of a linker has great impacts on biological activity, expression yield, and pharmacokinetic properties of a fusion partner (see Chen et al. Adv. Drug Deliv. Rev. 65:1357-1369, 2013).
Verdine et al (Methods in Enzymology, 2012, vol.503, 3-33) also showed or described possible unpredictability in staples (or linkers) in the peptide conjugates [see sections 3-5 and 13-14].
In view of above evidences, applicants have claimed broad range of conjugates (claimed formula I) and a skilled person in the art can expect unpredictability in the broadly claimed genus. There are no physical/chemical/structural features that applicants have tied to this property in a relevant teaching manner, making it impossible for an individual of ordinary skill in the art to determine which of the very large genus of claimed conjugates (claimed formula I) would be effective in retaining properties. Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement.
Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure species to make and possibly use of the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.”
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claimed subject matter and does not reasonably convey to one skilled in the relevant art that the inventors had possession of the entire scope of the claimed invention.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658