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:
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Information Disclosure Statement
The 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 amended claims 1-2, 11, 47, 54, 63 and 73-80 in the reply filed on 09/18/2025 is acknowledged.
The examiner also acknowledges applicants response to election of species and providing a single species for the claimed polypeptide.
It appears that applicants elected polypeptide is free of art and therefore, the search has been extended to the full scope of polypeptide with the recited sequences. No peptide is found in the art, which falls within the scope of the recited sequences.
Following an extensive search and examination, the originally elected species has been deemed free of the prior art. Per MPEP § 803.02, “If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended”. Accordingly, Examination has proceeded to the broadest genus of record as set forth at instant claim 1. The broadest genus has been rejected under 35 USC 112(a) as explained below.
Claims 57-60 and 64 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 1-2, 11, 47, 54, 63 and 73-80 are examined on merits in this office action.
Claim objections
Claim 1 is objected to because of the following informalities: the cited “SEQ ID NOS” should be changed to “SEQ ID NOs”. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: the cited “interface residues” should be changed to “interface residues on SARS-CoV-2 Spike glycoprotein RBD”, and delete ‘reference’ in the lines 4-5, for clarify purposes. Appropriate correction is required.
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 1-2, 11, 47, 54, 63 and 73-80 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:
Claim 1 is drawn to a polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 1-17, 19- 21, 23-34 and 100-101, wherein the polypeptide binds to SARS-CoV-2 Spike glycoprotein receptor binding domain (RBD).
Dependent claims, define and characterize the claimed polypeptide with the recited limitations or sequences. Specifically, claimed polypeptide further comprises functional domains and stabilization domains in it.
Based on the claim language, one of the claimed sequence is at least 80% identical to one of the claimed SEQ ID NOs: 1-17, 19-21, 23-34 and 100-101, which is part of the broadly claimed polypeptide, since the term “comprising” in the claim language does not exclude additional sequences or components in the claimed polypeptide. In addition, claims are associated with the recited property, which is ‘binds to SARS-Co-V-2 Spike glycoprotein RBD.
In the claimed SEQ ID NOs, length of amino acid sequences varies form 55 amino acids to 85 amino acids. The 20% of these sequences varies from 11 to 17 amino acids, and these can be any amino acids in any combinations and in any direction.
Additional functional domain and stabilization domain as claimed can be any sequence without any structural features. These domains can be located or bound anywhere in the claimed sequences of claim 1 with or without a linker.
So, in light of divergency in the claimed subject matter, it appears that there is no defined structure for the claimed polypeptide, and not even for the claimed sequences. The structural features are responsible for the property of the polypeptide, and in its absence of clear definition makes the claimed invention unpredictable, and cannot be envisioned by a skilled person in the art.
To support the above claimed subject matter, applicants specification showed or generated Ki values based on computational protein design to generate high affinity binders to the RDB of SARS-CoV-2 that blocks the interaction with the Ace2 receptor required for cell entry. Further exemplified with polypeptides, viz., LCB1-Fc, wherein Fc is functional domain, and LCB1v1.3. It is not clear what SEQ ID represents LCB1 [probably SEQ ID NOs: 1-4 as per specification in page 10]. It appears that, SEQ ID NO:8 represents LCBv1.3. It also appears that shown data is 100% of cited sequence(s) in claim 1 and no data is shown with 80% or above sequence identity. There is no description in the specification on ‘how the shown data’ can be extrapolated to other divergent species in the broadly claimed polypeptide. So, the specification has not adequately shown sufficient description or examples for broadly claimed subject matter, to show possession of the invention as claimed. In other words, applicants have not described the structure required to meet the cited functional limitation.
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 in the function/property 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, it makes the invention unpredictable, and cannot be envisioned by a skilled person in the art. In this case, structural features and limitations of claimed polypeptide are not defined or described, and so, a skilled person in the art would not know whether claimed polypeptide binds to SARS-CoV-2 Spike glycoprotein receptor RBD.
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 claimed polypeptide, 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 define complete structural features of polypeptide, will claimed polypeptide be capable of retaining its property? Do applicants provide enough description for all the variable in the polypeptide and their association towards its 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:
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:
Shown data is limited to polypeptides, viz., LCB1-Fc, wherein Fc is functional domain, and LCB1v1.3. It is not clear what SEQ ID represents LCB1 [probably SEQ ID NOs: 1-4 as per specification in page 10]. It appears that, SEQ ID NO:8 represents LCBv1.3. It also appears that shown data is 100% of cited sequence(s) in claim 1 and no data is shown with sequences having 80% or above sequence identity.
No description is provided for complete structure of claimed polypeptide. It is also not clear or not described where the functional and stabilization domains binds to the claimed sequences.
There is no description in the specification on ‘how the shown data’ can be extrapolated to other divergent species in the broadly claimed polypeptide. So, the specification has not adequately shown sufficient description or examples for broadly claimed subject matter, to show possession of the invention as claimed. In other words, applicants have not described the structure required to meet the cited functional limitation.
(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:
Fig.1-4 and 15 are simulated data for the polypeptides. In Fig. 5-15, shown data limited to polypeptides, viz., LCB1-Fc, wherein Fc is functional domain, and LCB1v1.3, as shown Fig. 5-14 and 16-17. As explained above, it appears that shown data is 100% of cited sequence(s) in claim 1 and no data is shown with sequences having 80% or above sequence identity.
No structural features or characterization of polypeptides is described 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:
As explained above, the recited sequences with specific SEQ ID NOs are part of claimed polypeptide, and the remaining part can have any sequence or other components. If it is amino acid sequence, then it may influence the property of sequences and eventually polypeptide as a whole, because divergent amino acids show divergent properties since protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. 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 polypeptides are unpredictable in light of divergent sequence in the remaining 20% or less in the claimed sequences, and so, 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 the recited property in a relevant teaching manner, which makes it impossible for an individual of ordinary skill in the art to determine which of the very large genus of polypeptides 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.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658