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 .
Priority
Acknowledgments are made that this application claims the priority to the following:
PNG
media_image1.png
56
383
media_image1.png
Greyscale
.
Information Disclosure Statement
Filed information disclosure statements (IDS) 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.
Response to Restriction
Applicant's response to restriction requirement and election of group I corresponding to claims 1-11 and newly added claims 33-34, without traverse, in the reply filed on 03/31/2026 is acknowledged.
Examiner also acknowledges applicants cancelation of claims 12-20.
So, only pending claims 1-11 and 33-34 are examined on merits in this office action.
Claim objections
Claim 11 is objected to because of the following informalities: claim depends on itself. Should depends on claim 10. Appropriate correction is required.
Claim Rejections - 35 USC§ 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.-Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 33-34 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
To establish whether a claim is properly dependent upon another claim, the claims must refer to a previously presented claim and then specify a further limitation of the subject matter claimed. A dependent claim does not lack compliance with 35 U.S.C. 112, fourth paragraph, simply because there is a question as to (1) the significance of the further limitation added by the dependent claim, or (2) whether the further limitation in fact changes the scope of the dependent claim from that of the claim from which it depends.
In the present case, claims 33-34 define X1 as an L-amino acid and D-amino acid., which are broader in scope to that of corresponding definition of X1 in claim 1. Accordingly, the dependent claims 33-34 do not narrow down the scope of independent claims and in fact dependent claims significantly broaden the scope.
Applicant may cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 and 33-34 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 peptide composition comprising anionic and cationic peptides, wherein the anionic peptides comprise recited Formula 1 or Formula 3, and the cationic peptides comprise recited Formula 2 or Formula 4, wherein
PNG
media_image2.png
98
570
media_image2.png
Greyscale
, wherein XA is anionic amino acid, XC is cationic amino acid, both ranges from 0-10; n and m from X1 and X2 ranges from 1-10; X1 is defined with the recited tryptophan derivatives and X2 can be any amino acid;
wherein the anionic and cationic peptides having Formula 1 and Formula 2 are able to self-assemble, and the anionic and cationic peptides having Formula 3 and Formula 4 are able to self-assemble into a nanofiber when the peptide composition is subjected to a self-assembly-stimulating condition.
In the above claim, the term “comprising” is an open language and does not exclude other components in the composition and also in the anionic and cationic peptide. In addition, total length of above sequences range from 5 to 42 amino acids, and since in light of term “comprise” the total length of peptide can be any length. At least based on X2, which can be any amino acid, the formulas can generate several hundreds of divergent sequences. Further, according to claim language, claimed composition can be in any form and can be in divergent conditions.
Dependent claims further narrow down the broadly claimed variables in claim 1, into the recited species and pH range for the composition.
Dependent claims further limit or define cationic and/or anionic as conjugates with cargo molecule or capping groups. Cargo can be any chemical moiety.
The above broadly claimed subject matter is associated with the recited property in the claim 1.
To support the above broadly claimed subject matter, applicants exemplified or described with 6 amino acid peptide pairs, viz., [AA], [WW] and [II] in shown examples, and [AA] did not appear to form an organized structure. In example 3 conjugate is limited to OVA[II], and it appears that there is a linker in between these two moieties. No data is shown or described the properties of any other sequences.
So, the issue is in the scope of the broadly claimed subject matter in all possible combinations. Specification failed to describe the nexus between shown data and broadly claimed subject matter. In other words, the structure/function relationship for the claimed generic variables and claimed subject matter is not described.
Applicants can claim as broadly as possible for the claimed invention. However, if there is a divergency in the genus or broadly claimed subject matter, and if it expects unpredictability for the claimed method, 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 method. In this case, at least protein chemistry is probably one of the most unpredictable areas of biotechnology and consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Similar, other components conditions of composition are also critical to retain the property of the composition. So, in 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.
The question is with thousands of possible divergent species in all possible combinations and no specific limitations on composition, (i) did applicants provide enough description for making all possible peptides, with all possible combinations? (ii) will the these be capable of retain its property of self-assembly? Based (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. Specification describes a theoretical approach for the claimed composition and peptides. Tables 1-4 describes subgenus of peptides and Table 5 describes specific 6 amino acid length peptides. Specification failed to defined complete sequence or structure of claimed peptides, in light of term “comprise” in the claim language. Exemplified or described claimed subject matter is limited to 6 amino acid length peptide pairs, viz., [AA], [WW] and [II], and interestingly, [AA] did not appear to form an organized structure. In example 3 describes conjugate, however it is limited OVA[II], and it appears that there is a linker in between OVA and [II]. So, it appears that linker is also required in the formation of conjugate. No description is provided on linkers. No description is also provided for cargo moiety. No description is provided for the stimulating condition(s) for the composition to form a nanofiber.
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:
Figures are very generic and limited.
Fig.1-5A represent the theoretical representation or description of sequences.
Fig.5B is exemplified data, but limited to AA, II and WW self-assembling peptide sets and their nanofibers shown in Fig.5C. No nanofiber formation is seen for AA.
Fig.6A-6E describes data from Example 2, but limited to WW and II.
Fig.8 and 9 describe the data from Example 3, but limited to conjugate of II and OVA.
So, as evidenced from the above description of drawings, it is clear that the claimed invention is not complete 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.
(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:
At least, in the broadly claimed peptides, which can have all possible combination of amino acids in their sequences, a skilled person in the art cannot envision applicants claimed composition and its associated property, since protein chemistry and peptide conformations are probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted.
For example, Pugliese [Trends in Biotechnology, Feb 2017, vol.25, No.2, 145-158] in review article describes current limitations/hurdles and unpredictability in their properties [see Abstract and Outstanding Questions in page 155].
Gao [Pharmaceutics, 2023, 15, 482, 1-20] describes the factors affecting peptide self-assembly [see section 3 in pages 3-5], such as charged amino acids, solvent, pH, temperature, ion concentration etc.
Based on above art, it appears that conditions are critical for the formation of self-assembly. However, no such limitations are present in the claimed subject matter.
In addition, substitution of amino acids or incorporation of amino acid sequence etc., can change the property of peptide and its conformation, which can be a hurdle for the formation of self-assembly and then nanofiber.
For example, Bowie et al (Science, 1990, 247:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (column 1, page 1306). Bowie et al further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
With regard to linkers, 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]. 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).
In view of above evidences, applicants have claimed wide range of peptides and all possible combinations, 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 peptides would be effective. 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
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
Prosecution Insights