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 application
Receipt of applicant’s remarks and claim amendments filed on 05/23/2025 are acknowledged.
For reasons internal to the USPTO, this application has been reassigned. The present examiner regrets if this is inconvenient to applicant(s).
The previous rejections have been withdrawn, and herewith prosecution has been reopened. A new non-final office action follows.
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.
Claim 19 is 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 pre-AIA the applicant regards as the invention.
Claim 19 recites “stable” in the claim language. The word “stable” is a relative word. It is not clear what the “stable”, specifically stable relative to what? Is it stable against specific enzymes or temperature or aqueous medium etc.? In addition the specification fails to define it or provide its definition.
In absence of its clear definition, the metes and bounds of the claim cannot be determined. Accordingly, claim is rendered indefinite.
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 1-11 , 15 and 17-21 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 a conjugate or a pharmaceutically acceptable salt thereof comprising at least one moiety -D conjugated via at least one moiety -L1-L2- to at least one moiety Z, wherein a moiety -L1- is conjugated to a π-electron-pair-donating heteroaromatic N of a moiety -D and wherein the linkage between -D and -L1- is reversible and wherein a moiety -L2- is conjugated to Z, wherein each -D is independently a π-electron-pair-donating heteroaromatic N-comprising moiety of a drug D-H; each -L2- is independently a single bond or a spacer moiety; each Z is independently a polymeric moiety or a C8-24 alkyl; each -L1- is independently of formula (I), with the recited definitions for the variables.
Dependent claims further limit the variables of independent claim with the recited sub-genus species.
No claim recites species for the claimed conjugate, and/or species for any variables in the claimed conjugate.
In the claims, the term “comprising” is an open language and does not exclude other components in the claimed conjugate. The recited “at least moiety” means one or more moieties, and it can be unlimited. The drug D can be any drug having π-electron-pair-donating heteroaromatic N of a moiety -D, or in other words, it can have any heteroaromatic ring comprising -N- atom or drug can be a peptide or protien. At least based on the definition of R1, “the group L1” can generate several hundreds of divergent species. L2 can be any spacer moiety or defined by subgenus in claim 20 which can generate several hundreds of spacers or linkers. Similarly, Z can be any polymeric moiety or defined by subgenus in claims 4-11, which can generate several hundreds of Zs. R1 ranges from simple H to complex heterocyclic moieties.
There is a functional language in the claimed subject matter, i.e., reversible linkage between D and L1, and linkage between Z and L2 is stable etc., in addition to the property of the conjugate. According to specification, the function, i.e. the cleavage of a moiety -D from the claimed conjugate, is mainly dependent on the nature of -L1- connecting -D to -L2-. As such, it can reasonably be expected that any encompassed moiety -D connected to -L1- via a 2-electron-pair-donating heteroaromatic N results in a reversible bond according to the present application.
To support the above broadly claimed subject matter, specification exemplified or described single species for L1, wherein R1 is H, Y is O, R2 is -CH2-CH3, which is a critical component for the broadly claimed subject matter, according to applicants specification. Further, a π-electron-pair-donating heteroaromatic N-comprising moiety of a drug, which is also critical component, is also exemplified with a single species, viz., indole ring. Similarly, L2 is exemplified with single species. It appears that drug is exemplified with two species. Preparative methods are also limited to these single species. [See Examples 5, 22-25, 29 and 31].
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 (works or may not work) for the claimed subject matter, then specification must describe the genus with divergent species, so that a skilled person in the art can understands claimed invention and can reproduce applicants claimed invention. In this case, at least divergent nature of broadly claimed L1 and L2 and π-electron-pair-donating heteroaromatic N-comprising moiety of a drug are probably one of the most unpredictable areas and consequently, the effects of dissimilarities and so, function of conjugate cannot be predicted. So, the absence of description with divergent species 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.
(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 subject matter can generate unlimited number of conjugates, whereas specification described limited species, their synthetic methods and their properties.
According to claim language and specification, one of the critical components is L1, however, specification exemplified or described with a single species for L1, wherein R1 is H, Y is O, R2 is -CH2-CH3. Second critical component is a π-electron-pair-donating heteroaromatic N-comprising moiety of a drug, is also exemplified with a single species, viz., indole ring. Similarly, L2 is exemplified with single species. Preparative methods are very limited.
There is no evidence or description is provided to support ‘shown single species can be extrapolated to broadly claimed subject matter’.
So, the provided data evidence for the broadly claimed subject matter 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 diagrams are Figures are shown 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:
First, the synthetic methodology described in the disclosure is very generic and may not be applicable to make all possible conjugates. See In re Marzocchi and Horton 169 USPQ 367 3.
Second, linkers or spacers are critical for the claimed conjugates. Release of drug is sensitive to the chemical nature of spacer. In the broadly claimed L1, if R1 is H, which is expected to behave different from if R1 in L1 is complex heterocyclic ring, at least based on bulky chemical nature. Similarly, side chains on drug or size of drug may influence on overall property of conjugate.
In addition, in the claimed conjugates, the drug can be a peptide or protein [see claim 2], and so, the properties of conjugates 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 (aka spacer or staple etc.) 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 in the peptide conjugates [see sections 3-5 and 13-14].
In view of above, applicants have claimed unlimited range of compounds. 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 compounds or conjugates would be effective in retaining their end 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
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.
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, 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.
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.
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
