The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election of Group I, claims 1-11, 15, to SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915, in the reply filed on August 13, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 12-14, 16 have been withdrawn from consideration by the examiner because they are drawn to non-elected inventions. Claims 1-11, 15, to SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915, are under consideration.
Priority: This application claims benefit of provisional application 63/255355, filed October 13, 2021.
Claim Rejections - 35 USC § 112
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 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. 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The factors considered in the Written Description requirement are (1) Actual reduction to practice; (2) Disclosure of drawings or structural chemical formulas; (3) Sufficient relevant identifying characteristics; (4) Method of making the claimed invention; (5) Level of skill and knowledge in the art; and (6) Predictability in the art. 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.
Claim 1 and its dependent claims are directed to “a polypeptide comprising an amino acid sequence that is at least 50% (claim 1, 4-7, 15), or 75% (claim 2) or 90% (claim 3) identical to the amino acid sequence of a polypeptide of SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915 (elected species) wherein claims 8-10, 11 are directed to a homodimer assembled from a plurality of the “polypeptide”. The claims, as written, include the structural variants resulting from said 50%, 75% or 90% (genus) which encompass the variants of structure alterations of 50%, 25% or 10%, respectively, from the full-length sequence of the noted SEQ ID NOS., wherein said “variants” (genus) can be generated from any mutations or alterations generated from substitutions, deletions and/or insertions and wherein “a polypeptide” is given its broadest reasonable interpretation as being drawn to a subsequence of any fragment of the full-length sequence thereof.
The specification does not describe any members of the claimed genus by complete structure.
Although the specification describes that the computationally designed “polypeptide” is for characterizing and designing homodimers that are hyperstable for binding C2 symmetric ligands (at least paragraphs 0044-0050 of the application publication), the instant disclosure does not describe the structure for substitution variants, deletion variants or insertion variants of the noted SEQ ID NOS. The specification does not describe the physical or chemical characteristics for substitution variants, deletion variants or insertion variants of the elected SEQ ID NOS. recited in the claims. The specification does not disclose any correlation(s) between the structure of the variants and the elected SEQ ID NOS., or any correlation(s) of structure with variant function. Although the specification states that these types of amino acid changes are routinely made in the art, the specification and claims do not describe any specific changes to be made. No common structural attributes identify the members of the substitution, deletion and insertion variant genus. Because the disclosure fails to describe the common attributes or characteristics that identify substitution, deletion and insertion variant members of the genus, and because the genus is highly variant, the elected SEQ ID NOS. are insufficient to describe the genus and insufficient to describe any homodimer comprising a ligand, specifically all C2 symmetric compounds.
It is known that while designing de novo proteins is improving rapidly, significant challenges remain; chief amongst these is the need to deliver functional de novo proteins; solving such problems will require more than simply adding functional side chains to extant de novo structures (Dawson et al. p. 102). The robust and routine design of functional de novo proteins remains an unsolved mystery; there are no examples of tight binding of small, polar molecules by de novo proteins (p. 107).
The MPEP notes that “[A] “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus; and state that [A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.” (see MPEP 2163 II A.3 (a) (ii)). In this case, there is substantial variation within the claimed “genus” and the instant specification does not provide a sufficient species to represent the genus of claimed “variants”, so as to satisfy the written description requirement under 35 USC 112(a).
Accordingly, one of skill in the art would not recognize that applicants have been in possession of claimed genus. The claimed subject matter “polypeptide (which is based on the computational design) is not supported by an adequate written description because a representative number of species has not been described.
Therefore, the specification does not satisfy written description under USC 112(a) with respect to the full scope of claims 1-11, 15.
Claims 1-11, 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915, and homodimers comprising the noted polypeptide, does not reasonably provide enablement for variants of the noted polypeptides comprising an amino acid sequence at least 50% identical, 75% identical, 90% identical to the recited SEQ ID NOS., and homodimers comprising one or more of the polypeptides. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be the most relevant to the instant rejection are addressed below.
(A) The scope of the claims/(B)The nature of the invention:
Claim 1 and its dependent claims are directed to “a polypeptide comprising an amino acid sequence that is at least 50% (claim 1, 4-7, 15), or 75% (claim 2) or 90% (claim 3) identical to the amino acid sequence of a polypeptide of SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915 (elected species) wherein claims 8-10, 11 are directed to a homodimer assembled from a plurality of the “polypeptide”. The claims, as written, include the structural variants resulting from said 50%, 75% or 90%, which encompass the variants of structure alterations of 50%, 25% or 10%, respectively, from the full-length sequence of the noted SEQ ID NOS., wherein said “variants” can be generated from any mutations or alterations generated from substitutions, deletions and/or insertions and wherein “a polypeptide” is given its broadest reasonable interpretation as being drawn to a subsequence of any fragment of the full-length sequence thereof. The specification describes that the computationally designed “polypeptide” is for characterizing and designing homodimers that are hyperstable for binding C2 symmetric ligands (at least paragraphs 0044-0050 of the application publication). However, the instant disclosure does not describe the structure for substitution variants, deletion variants or insertion variants of the noted SEQ ID NOS. The specification does not describe the physical or chemical characteristics for substitution variants, deletion variants or insertion variants of the elected SEQ ID NOS. recited in the claims. The specification does not disclose any correlation(s) between the structure of the variants and the elected SEQ ID NOS., or any correlation(s) of structure with variant function. The specification fails to provide enabling for making and using the said “variants” correlated with a particular biological application. In the absence of the function or property as to the claimed “polypeptide”, it would require undue experimentation to identify and characterize the claimed “variant” polypeptide and whether it is capable of forming a stable homodimer that binds all ligands, including any C2 symmetric compound.
(C) The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability.”
It is known that while designing de novo proteins is improving rapidly, significant challenges remain; chief amongst these is the need to deliver functional de novo proteins; solving such problems will require more than simply adding functional side chains to extant de novo structures (Dawson et al. p. 102). The robust and routine design of functional de novo proteins remains an unsolved mystery; there are no examples of tight binding of small, polar molecules by de novo proteins (p. 107).
“[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.” See MPEP § 2164.03.
(F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In the instant case the quantity of experimentation would be large and undue since there are myriad substitutions and/or deletions and/or additions and amino acid residues to choose from to obtain variants of any recited SEQ ID NO. that will have stability and functionality to form a highly stable homodimer capable of binding any ligand, including any C2 symmetric compound. The specification discloses the computational ability to generate polypeptides to form C2 symmetric protein homodimers and their potential for further characterization and capability of binding C2 symmetric compounds (at least paragraphs 0044-0050 of the application publication), however, the specification fails to disclose any variant of the computationally generated polypeptides able to form a stable homodimer that binds any ligand or C2 symmetric compound. There is no guidance regarding which 50%, 25%, 10% may vary from the recited SEQ ID NOS. (at least claims 1-3). The specification does not disclose any particular variants of any of the designed polypeptides comprising an amino acid sequence at least 50% identical to the amino acid sequence selected from the recited SEQ ID NOS, having any substitutions and/or deletions and/or additions, having the stability and functionality to form a stable homodimer that binds any ligand or C2 symmetric compound.
The nature of the invention is such that many designed polypeptides that are substantially similar may or may not have the stability and functionality to form a highly stable homodimer capable of binding any ligand or any C2 symmetric compound. The state of the prior art is that the robust and routine design of functional de novo proteins remains an unsolved mystery; there are no examples of tight binding of small, polar molecules by de novo proteins (Dawson et al. p. 107). The relative level of skill in this art is very high. It would require an undue burden of experimentation for a skilled artisan to determine exactly which derivatives and/or variants have sufficient stability and function to form a homodimer having stability to bind any ligand and any C2 symmetric compound. The predictability as to which designed polypeptide having the stability and desired function for productivity is zero.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, and the high degree of unpredictability as evidenced by the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention.
When the factors are considered in their entirety, the Wands analysis dictates a finding of undue experimentation and thus, the claims are not enabled.
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.
Claims 1-11, 15 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-3 recite the polypeptide comprises an amino acid sequence at least 50%, 75%, and 90% “identical” to the recited SEQ ID NOS. It is not clear what is meant by “identical”, i.e. whether identical is referring to sequence identity, functionality, activity, etc. Further, something is either identical or not; it is not clear how it only be partially identical. Further clarification and/or correction is requested.
Claims 1-4 recite the terms “added fused”. The claims should clarify what is meant by added fused. Additionally, it is not clear whether the elements recited in the parentheses are a part of the claims. Further clarification and/or correction is requested.
Claims 5-6 recite the limitation "the reference polypeptide" in the claim. There is insufficient antecedent basis for this limitation in the claim. It is also not clear what the reference polypeptide is. Further clarification is requested.
Claims 7-11, 15 are included in this rejection because they are dependent on the above claim(s).
The elected SEQ ID NOS: 2275, 41, 303, 429, 634, 1073, 1192, 1884, 1987, 2915 appear to be free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marsha Tsay/Primary Examiner, Art Unit 1656