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 4th Feb 2026 are acknowledged.
In light of claim amendments and cancelation of claims 1-9, previous 112(b) and 102 rejections are withdrawn.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 arguments below.
Response to Arguments
Applicants’ argue that the SEQ ID NOs: 1-102 have a common structure and function.
Applicants pointed to a general formula 1 (SEQ ID NO:103), which is very generic and can produce thousands of peptides with various combinations of recited amino acids. Core structure refers to common or functionally similar chemical groups, which is critical for its function. For example, 10 amino acids domain in a given 50 amino acid peptide (1st peptide) is critical for its property. If Glu is replaced with Asp in the domain, and the resulting peptide (2nd peptide) is expected to behave similarly since both Glu and Asp are structurally similar, and so, two peptides have common core. However, in the SEQ ID NO:103, each variable, in Xaa1 to Xaa30, have divergent amino acids, which cannot make a common core and so, common property cannot be expected.
In the SEQ ID:1-102, some have ring structures and some are linear, and so, these are structurally not similar. Shown data in Table 2 ranges from zero or fraction percentage to 200+ percentage, which implied that there is also no common property. Accordingly, SEQ ID NO:103 cannot be a common core or common structure.
Applicants argue that the therapeutic effect of the long-acting conjugate of SEQ ID NO: 42 for vasculitis can be extended to the remaining 101 sequences.
For the claimed method, shown data is limited to conjugate of SEQ ID NO:42 in Example 3. No data is shown with other sequences. So, applicants arguments are simple statements, without any evidence. In the written description rejection, examiner explained with evidences that single amino acid change may result in loss of property of a peptide. Moreover, cited sequences in Table 2 shows divergent properties. Even in shown data in Table 3 show divergent values. Accordingly, in absence of evidences, shown data cannot be extrapolated to the remaining 101 sequences.
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 12-22 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 product. 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 12 is drawn to a method for preventing or treating vasculitis in a subject in need thereof, the method comprising administering to the subject an effective amount of a pharmaceutical composition: a pharmaceutically acceptable excipient; and a pharmaceutically effective amount of a peptide comprising an amino acid sequence of any one of SEQ ID NOs: 1 to 102.
Dependent claims 13-14 limit the peptide to the recited conjugate form and amidated form.
Dependent claims 15-17 narrow down the peptide to the recited SEQ IDs.
Dependent claim 18 define ring structure for claimed peptide(s).
Dependent claim 19 defines the molecular weight of ethylene glycol repeating units in the conjugate.
Dependent claim 20 defines F as an IgG Fc region in the conjugate.
Dependent claims 21-22 define vasculitis for the claimed method.
Based on the above claimed languages, claims 12, 14-18 and 21-22 require just administration of recited sequence(s) in the form of pharmaceutical composition and do not require in the form of conjugate. Some of the sequences do not even have ring structure. Claims 13 and 19-20 require peptide in the form of recited conjugates. It appears that recited sequences do not have common core structure. The term “comprising”, which is open-ended language, does not exclude additional sequences or components in the recited sequences. In addition, “preventing” means complete eradication of claimed vasculitis, both existing as well as from the future occurrences. Subject and dosage amounts are very generic and claims read all possible modes of administrations.
To support the above claimed subject matter, applicants specification exemplified the claimed method with SEQ ID NO:42, which is in the form of conjugate and also comprises a ring structure in it. No data is shown with any other sequences for treating or preventing vasculitis. There is no description in the specification on ‘how the shown data’ can be extrapolated to the recited sequences and to make the claimed method. No data or description is provided to support claimed “preventing vasculitis”. So, the specification has not adequately shown sufficient description or examples for broadly claimed subject matter, to show possession of the invention as claimed.
Applicants can claim as broadly as possible for the claimed invention. However, if there is a variability in the broadly claimed subject matter, and if the variability expects unpredictability or uncertainties for the claimed subject matter, then specification must describe/clarify the nexus between shown data and the broadly claimed subject matter, so that a skilled person in the art can understands the invention and can reproduce applicants claimed invention. In its absence the invention cannot be envisioned by a skilled person in the art. In this case, structural features and limitations of claimed peptides are not defined, and so, a skilled person in the art would not know whether claimed peptide treats or prevents vasculitis.
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, in this case lack of structural features of recited peptide, 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 (MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The issue at question is in absence of defined structural features of recited peptides and its conjugates, will claimed peptides be capable of retaining its property? Do applicants provide enough description for all the variable in the recited peptides and their association towards the end property, so that a skilled person in the art understands 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:
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:
Description in the specification is limited to sequences and the definitions of variables in it. Shown data is limited to the conjugate of SEQ ID NO:42 in experimental example 2. Table 2 shows relative titers compared to human GLP-1, GCG and GIP are shown for SEQ ID NO:1-102, not conjugates. Similar data is shown in Table 3 for long-acting conjugates of SEQ ID NOs: 21-22, 42-43, 50, 77 and 96. Huge variability can be seen in the shown data in Tables 2-3 for the recited peptides.
There is no description in the specification on ‘how the shown data’ can be extrapolated to the recited sequences and to make the claimed method. No data or description is provided to support claimed “preventing vasculitis”.
So, the specification has not adequately shown sufficient description or examples for broadly claimed subject matter, to show possession of the invention as claimed.
(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 also limited to the conjugate of SEQ ID NO:42. No data or structural features of complete structure of peptide is provided for treating vasculitis.
(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:
Divergent amino acids show divergent properties and so, protein chemistry is probably one of the most unpredictable areas of biotechnology. In this case, specification described recited sequences into a general formula I, wherein each variable can be represented by several divergent amino acids. Consequently, 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, properties of broadly claimed peptide are unpredictable and a skilled person in the art cannot envision applicants claimed subject matter. Also, 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 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
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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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658