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 .
DETAILED ACTION
Response to Election/Restriction filed on April 24, 2026 is acknowledged. Claims 1-39, 49, 52, 62 were canceled, claims 41, 44-48, 51, 57-61 were amended and claims 40-48, 50-51, 53-61 are pending in the instant application.
Election/Restrictions
Applicant elected with traverse Group I (directed to polypeptides, claims 40-44) and with traverse SEQ ID NO:1 from List I in the reply filed April 24, 2026.
Applicants argue that all claimed inventions share a single general inventive concept that is not taught by the prior art. Applicant argues that the polypeptide recited in amended claim 1 has a molecular weight of approximately 32 kda. In contrast, the molecular weight of Violaxanthin de epoxidase is 39.9 kDA. Furthermore, claim 41 was amended to recite specific sequences including peptides having at least 85% sequence identity to SEQ ID NO:1. Hieber does not teach a peptide having at least 85% sequence identity to SEQ ID NO:1. Applicants arguments have been fully considered but not found persuasive. First, Applicants are arguing limitations from claims that are canceled (i.e. claim 1 and a specific molecular weight). Thus, these arguments are moot. Furthermore, a restriction requirement is evaluated based on the claims pending at the time the requirement is made. Subsequent amendment, cancellation, or addition of claims does not retroactively affect the propriety of the original restriction requirement. The correctness of the restriction requirement is determined from the claim set that was before the examiner when the restriction was issued. See MPEP §§ 803 and 818. Amendments filed after the restriction requirement may alter the scope of examination going forward but do not render an otherwise proper restriction requirement improper. Nevertheless, given the amendment, claims 48, 50 (invention 3), 51, 53-55 (invention 4) are now combined with invention 1 (drawn to a polypeptide and compositions thereof).
The restriction is deemed proper and is made FINAL in this office action.
Claims 45-47, 56-61 are withdrawn from consideration as being drawn to a non-elected species and/or invention.
Claims 40-44, 48, 50-51, 53-55 are examined on the merits of this office action.
Sequence Compliance
This application fails to comply with the requirements of 37 C.F.R 1.821-1.825 for the reasons set forth on the attached Notice to Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821-1.825) before the application can be examined under 35 U.S.C 131 and 132. Each sequence disclosed must appear separately in the “Sequence Listing.” Each sequence set forth in the “Sequence Listing” must be assigned a separate sequence identifier. Applicant failed provide sequence listing and identifiers for the sequence found in instant claim 44.
Claim Objection
Claim 44 is objected to for the following reason: Claim 44 recites amino acid sequences. The peptide sequence is missing a sequence listing and respective sequence identifier (see 37 CFR 1.821(d)). This error should be corrected.
Specification Objection
The specification is objected to for containing referring to sequences without also identifying them by the sequence identifier assigned to them in the sequence listing as required by 37 CFR 1.821(d) (see page 5 for example). The specification discloses peptide sequences, and these are missing their respective sequence identifiers. For example, the sequence found on pages 14, 27, 30, 32, 34 and 41, disclose peptide sequences, but these are missing their sequence identifiers. The examiner would like to bring the applicant’s attention to the following excerpt from MPEP §2422.03:
37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application. This requirement is also intended to permit references, in both the description and claims, to sequences set forth in the "Sequence Listing" by the use of assigned sequence identifiers without repeating the sequence in the text of the description or claims. Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing." Where a sequence is embedded in the text of an application, it must be presented in a manner that complies with the requirements of the sequence rules.
This error should be corrected throughout the Applicant’s specification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 40-44, 48, 50-51, 53-55 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, Claims 40-44, 48, 50-51, 53-55 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below and is based on MPEP2106.03-MPEP2106.05.
Claim Interpretation
Claim 41 claims an isolated polypeptide possessing epoxy group removing catalytic activity and encompasses SEQ ID NO:1, variants having at least 85% sequence identity, partial sequences and chimeric sequences. Claims 43-44 encompass the same peptides including peptides having at least 85% sequence identity to SEQ ID NO:1. Claim 40 claims any polypeptide having epoxy group removing catalytic activity (which encompasses instant SEQ ID NO:1 variants as described in instant claim 41 and also naturally occurring GSTs).
Subject Matter Eligibility Test for Products and Processes
Step 1: Is the claim to a process, machine, manufacture, or composition of matter (see MPEP
2106.03)?
Yes, the instant claims are directed to a statutory patent-eligible subject matter category, namely a composition of matter.
Step 2A (1): Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea
(see 2106.04)?
Yes, the claims are directed to a natural phenomenon, namely naturally-occurring peptides. Specifically, there is evidence of record (see attached handout, Uniprot A0ABQ0CFG2) that identifies naturally occurring GST N-terminal containing protein from Epichloe bromicola comprising 280 amino acids and sharing 95.3 % sequence identity to SEQ ID NO:1.
Accordingly, the pending claims are directed to naturally occurring peptides.
As the product is found in nature, consideration is given to whether it is integrated into a practical application or contains other elements that provide a marked difference as compared to the natural counterpart.
Step 2A (2): Does the Claim recite additional Elements that integrate the judicial Exception into a Practical Application? (see MPEP 2106.04 (d)) NO. This judicial exception is not integrated into a practical application because it does not provide a treatment that affirmatively recites an action that effects a particular treatment for a disease or medical condition.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception (see MPEP 2106.05))?
No, the claim does not recite additional elements that amount to significantly more than the judicial exception, as explained below. Factors for determining if the claim directed to a product of nature, as a whole, recites something significantly more than the judicial exception, are provided in MPEP 2106. Claims 48, 50, 51, 53-55 contain additional limitations including pharmaceutical carriers, glutathione, food ingredients, feed ingredients, flour, grain products, fruit juices, dairy products and beverages which constitute routine and conventional formulation components. These limitations merely append conventional components to the naturally occurring protein and do not transform the claimed subject matter into patent eligible subject matter.
There is no evidence that the combination of the peptide any of these above components results in a different property or function of the peptide. The peptide of the instant claims does not amount to significantly more than the exception. Regarding the claimed activity of having epoxy group removing catalytic activity, the naturally occurring homolog (Uniprot A0ABQ0CFG2) has 95.3% sequence identity, conservation of the GST N-terminal domain, GST c-terminal domain and conservation of the catalytic domain and thus, it would be expected that the sequence would inherently have the claimed activity.
In sum, when the relevant considerations are analyzed, they weigh against a significant difference. Accordingly, Claims 40-44, 48, 50-51, 53-55 not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112, First Paragraph
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 40-44, 48, 50-51, 53-55 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
Claim 40 is directed to “An isolated polypeptide having epoxy group-removing catalytic activity, wherein the polypeptide is capable of catalyzing a reaction between an epoxy group of a trichothecene mycotoxin and glutathione in a PBS buffer at a temperature of 15°C to 35°C to produce a glutathionylated derivative” (claim 40). The claim is purely functional and is not limited to amino acid sequence, sequence identity, conserved motif, source organism, protein family, molecular weight, catalytic domain or any other structural feature. Claim 41 encompasses a broad genus of catalytic polypeptides comprising SEQ ID NO:1; sequences having at least 85% sequence identity, sequences containing one or more amino acid substitutions, active partial sequences and chimeric sequences. Because SEQ ID NO:1 contains approximately 281 amino acids, an 85% identity sequence may differ by approximately 42 amino acid residues while still failing within the claim. Claim 41 therefore encompasses an extremely large number of undisclosed proteins. Claim 44 claims an amino acid sequence formula with variable positions (V1-V3, X1-X8) and also includes 85% sequence identity.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. 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.
The specification demonstrates actual reduction to practice of specific embodiments. Specifically, Applicant discloses cloning of FTCD genes; recombinant expression in E.Coli; recombinant expression in E. Coli, Bacillus subtilis, lactobacillus; purification of recombinant proteins; catalytic activity assays and glutathione dependent detoxification of trichothecenes. The specification further demonstrates catalytic activity against DON; 3-ADON; 15-ADON; NIV; DAS; HT-2; T-2 and FUS-X. The office acknowledges that Applicant reduced certain FTCD embodiments to practice. However, reduction to practice of a limited number of species does not establish possession of an entire claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
Regarding claim 40 (and dependent claims); the specification primarily discloses a single enzyme family designated FTCD and variants derived therefrom. Although FTCD proteins are described in detail, the specification does not identify structural characteristics common to all polypeptides capable of catalyzing the claimed reaction. The specification does not identify a universally conserved catalytic motif, a universally conserved active site, a conserved fold, a catalytic residue set common to all catalytic proteins, a protein family encompassing all claimed polypeptides. Accordingly, the disclosure does not provide identifying structural characteristics sufficient to define the entire functional genus recited in claim 40. Regarding claim 41 (and dependent claims), SEQ ID NO:1, conserved residues, certain variable residues, truncation mutants, linker substitution mutants, specific amino acid substitutions. However, the disclosed examples only represent a small subset of the proteins encompassed by claim 41 (and claim 40). Claim 41 encompasses all proteins having at least 85% sequence identity to SEQ ID NO:1 regardless of where the sequence differences occur. The specification does not identify which of the approximately 281 positions may generally tolerate variation and which may not throughout the entire claimed genus. To the contrary, the mutagenesis data demonstrates that many substitution severely impair catalytic activity (examples include A98V, A99v, L101V T104S etc…). These data indicate that activity is highly sequence dependent. Consequently, the disclosure does not provide sufficient identifying characteristics to support the entire 85% identiy genus.
Physical/Chemical Properties
The specification discloses certain physical and chemical properties of FTCD proteins, including approximate molecular weight, soluble expression, catalytic activity in PBS buffer, formation of glutathione adducts and detoxification of trichothecene mycotoxins. However, these properties are disclosed only for the specific FTCD proteins and variants tested. The specification does not establish that all proteins encompassed by claims 40-41 possess the same structural or physicochemical characteristics. Nor does the specification provide evidence that proteins throughout the full scope of the claims share a common structural basis for catalytic activity. Accordingly, the disclosed physical and chemical properties do no demonstrate possession of the entire claimed genera.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification primarily defines the invention by function, epoxy group removing catalytic activity. However, functional language alone does not establish possession of a broad biological genus absent a demonstrated correlation between structure and function. Here, the specification demonstrates the opposite. The experimental data show that the amino acid substitutions can produce dramatically different outcomes where some substitutions retain activity, some reduce activity to very low levels. The specification expressly states that substitutions at positions 100 and 178 greatly affect activity. Thus, the disclosed data establish that catalytic activity is highly sensitive to sequence variation. Despite this unpredictability, the claims encompass all proteins having 85% identity and all proteins containing one or more mutations while maintaining activity. The specification provides no predictive rule enabling one of ordinary skill to determine which of the enormous number of possible variants will retain activity. Therefore, no adequate structure function relationship is disclosed of the full claimed genus.
Regarding claim 44, Although the specification discloses certain exemplified FTCD/de-epoxidase sequences and selected variants, claim 44 encompasses a broad genus of polypeptides defined by multiple variable amino acid positions (X1-X8) and three extensive variable regions (V1-V3) that may differ from SEQ ID NO: 1 by up to 15% while still falling within the claim scope. The specification does not disclose a representative number of species commensurate with the breadth of the claimed genus, nor does it identify common structural features sufficient to demonstrate possession of all proteins encompassed by the claim. Moreover, the experimental data show that amino acid substitutions can have markedly different effects on catalytic activity, including substantial reductions in activity at certain positions, demonstrating an unpredictable relationship between sequence variation and function. Accordingly, the specification does not reasonably convey to one of ordinary skill in the art that the inventors possessed the full scope of the genus recited in claim 44 at the time of filing.
Method of Making
The specification describes methods for cloning specific disclosed genes, expressing proteins in Bacillus subtilis, expressing proteins in lactobacillus and generating certain identified variants. However, disclosure of methods for making particular examples does not demonstrate possession of all proteins encompassed by the claims. The specification does not provide guidance sufficient to identify, obtain or recognize the full scope of all proteins having 85% identity, all mutant proteins, all active fragments, all active chimeric proteins, all proteins capable of catalyzing the claimed reaction. Therefore, the disclosed methods do not cure the written description deficiency.
Conclusion
In conclusion, only polypeptides, reduced to practice satisfies the written description requirements of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 112
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 41, 43-44, 48, 50-51, 53-55 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.
Claim 41 claims the term “original polypeptide activity”. This term is indefinite because it is unclear which activity constitutes the “original” activity. While claim 41 recites an isolated polypeptide having epoxy group removing catalytic activity, there are additional activities and properties of the peptide. Therefore, one of ordinary skill would not reasonably understand the scope of the claim. Claims 43-44, 48, 50-51, 53-55 are also rejected due to their dependence on claim 41 and not clarifying this point of confusion.
Claim 44 recites that “V1 is absent or represents a first variable region.” However, claim 44 depends from claim 41, and the scope of the claimed polypeptide is unclear when V1 is absent. In particular, claim 41(4) recites an N-terminal partial sequence, whereas an embodiment in which V1 is absent removes the N-terminal portion of SEQ ID NO:1 and appears to result in a C-terminal or internal fragment rather than an N-terminal partial sequence. Accordingly, it is unclear whether an embodiment in which V1 is absent falls within the scope of claim 41, and the metes and bounds of claim 44 cannot be determined with reasonable certainty.
Claim Rejections - 35 USC § 112
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 pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 44 is 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.
Claim 44 depends from claim 41 and claims a sequence comprising variable regions V1, V2, and V3. However, claim 44 additionally recites that V1 may be absent. When V1 is absent, the claimed sequence may begin at an internal region of SEQ ID NO:1 rather than constituting a partial consecutive sequence, including the preferred N-terminal partial consecutive sequence, recited in claim 41(4). Accordingly, claim 44 appears to encompass subject matter that is not necessarily within the scope of all embodiments of claim 41 and therefore does not clearly further limit the claim from which it depends.
Applicant may cancel the claim(s), 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 § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 40 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Subramanian (US6500639 B2).
Subramanian discloses isolated glutathione S transferase (GST) polypeptides useful for mycotoxin detoxification (claims 1 and 11). Subramanian further teaches detoxification of trichothecene mycotoxins, including reactions involving the epoxide moiety of the toxin and glutathione mediated detoxification (e.g. Col. 17-18). Because Claim 40 recites only an isolated polypeptide having epoxy group removing catalytic activity and imposes no structural limitation on the polypeptide, the GST polypeptides disclosed by Subramanian inherently possess the claimed activity of catalyzing a reaction between an epoxy group of a trichothecene mycotoxin and glutathione in PBS buffer at a temperature of 15-35 degrees Celsius to produce a glutathionylated derivative. Inherency may be established where a claimed property is necessarily present in the prior art subject matter, even if not expressly recognized. Accordingly, the GST polypeptides disclosed by Subramanian fall within the scope of claim 40.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
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