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
Filed 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 amended claims 1, 17 and 21-34, with traverse, in the reply filed on 06/18/2026 is acknowledged.
Applicants’ traversal of restriction is on the ground(s) that there would not be no additional search burden to search all claims.
The search strategy for polypeptide is different from that of fusion protein, scaffold, nucleic acid, vector and host cell. The polypeptide search is based on the on its structure, whereas the search of fusion proteins and other groups claims requires additional key words or subject matter, which is a serious burden. Even if the product is allowable, the claims of other groups are not necessarily be allowable, because these claims will be analyzed in view of 112 issues, which requires an additional search.
Accordingly, the restriction requirement made on 04/21/2026 is proper.
Claims 9 and 13-16 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
The claims 1, 17 and 21-34 are examined on merits in this office action.
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, 17 and 21-34 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 polypeptide comprising an amino acid sequence at least 35% identical to the amino acid sequence of SEQ ID NO:1457 with the recited limitations.
Dependent claims are drawn to pharmaceutical composition of polypeptide of claim 1 and the specific amino acids at specific positions.
The term “comprising” is an open language and does not exclude other components in the claimed polypeptide.
The SEQ ID NO:1457 is 60 amino acid polypeptide. Claimed polypeptide comprising at least 35% identical to sequence of SEQ ID NO:1457, which is ~21 amino acids, and remaining ~29 amino acids can be any amino acids and in all possible combinations and can be in anywhere in the SEQ ID NO:1457. For example, all remaining 29 amino acids can be negatively or positively charged or hydrophobic or all can be prolines or cysteines etc.
Specification define the property of claimed polypeptide as a “protein binding” polypeptide and describes its binding properties towards CD3D, EGFR, FGFR, H3, IGF1R, IL7R, insulinR, PDGFR, TGF-beta, Tie2, TrkA and VirB8 proteins. Claimed SEQ ID NO:1457 is defined as TrkA binding polypeptide.
To support above claimed subject matter, specification in Table 13FFF describes possible amino acid substitutions in SEQ ID NO:1457 with best and tolerable amino acids. In Table shown in page 180, describes SEQ ID NO:1457 as a target for TrkA, and further it simply say # mutations is 12, and there is no description on ‘where exactly these mutation located’.
In the above tables, the shown data is limited to 100% of SEQ ID NO:1457. No data is shown or described for 35% to 99% sequence identity. Also, there is no description on complete structural features of claimed polypeptide.
In light of above, (i) did applicants provide enough description for making sequences of 35% to 99% of sequences identity and remaining can be any possible amino acids with all possible combinations, and (ii) will these be capable of retain its defined property in the specification? Based on (i) and/or (ii), will a skilled person in the art understand the claimed invention?
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 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 polypeptide and can reproduce applicants claimed invention. In this case, 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. 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. Specification theoretically describes polypeptides and their properties. There is no experimental evidence is shown for the defined property of claimed SEQ ID NO:1457. In Table shown in page 180, describes SEQ ID NO:1457 as a target for TrkA, and further it simply say # mutations is 12, and there is no description on ‘where exactly these mutation are located’.
Description is limited to 100% of SEQ ID NO:1457. No data is shown or described for 35% to 99% sequence identity. Also, there is no description on complete structural features of claimed polypeptide.
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:
Drawings are limited to theoretical description of polypeptides and no actual evidence of their properties are shown. No description on 35% to 99% sequence identity polypeptides and no description on complete structural features of claimed polypeptide in the drawings.
(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 based on sequence identity, which can have at least 35% of SEQ ID NO:1457, in the claimed polypeptide, the effects of sequence dissimilarities upon protein structure and function cannot be predicted.
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.
In view of above, 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 polypeptides would be effective in retaining its 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.
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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
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