The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received May 13, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 12-14 are withdrawn. Claims 1-11, to peptide sequence AgOR1, are under consideration.
Priority: This application is a 371 of PCT/JP2021/027265, filed July 21, 2021, which claims benefit to foreign application JP 2020-126684, filed July 27, 2020. A copy of the foreign priority document has been received in the instant application on January 27, 2023, and is not in the English language.
Objections and Rejections
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 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.
In analyzing the claims for compliance with the written description requirements of 35 U.S.C. 112(a), a determination is made as to whether the specification contains a written description sufficient to show they had possession of the full scope of their claimed invention at the time the application was filed. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Claims 1-11 are drawn to a mutant-insect olfactory receptor protein, comprising amino acid sequence B composed of amino acid sequence A containing a mutation, wherein the amino acid sequence A is in a corresponding wild-type insect olfactory receptor protein and represented by formula (1): ɸ7X1X2Z1X3X4Z2Z3ɸ6Uɸ5ɸ4ɸ3ɸ2ɸ1X5X6 wherein X1 to X6 and Z1 to Z3 represent amino acids derived from the amino acid sequence of the wild-type insect olfactory receptor, ɸ1 represents a hydrophobic amino acid, ɸ2 to ɸ7 each independently represent an uncharged polar amino acid or a hydrophobic amino acid, and U represents an uncharged polar amino acid, and the mutant insect olfactory receptor satisfies at least one condition selected from the group consisting of the conditions (1) to (3), etc., nucleic acid molecules encoding the mutant-insect olfactory receptor protein, and a cell comprising the nucleic acid molecules.
Accordingly, the claims encompass a significantly large genus of mutant insect olfactory receptor proteins, nucleic molecules encoding the mutant insect olfactory receptor proteins, and cells comprising the nucleic acid molecules. The recited genus of mutant insect olfactory receptor proteins are defined through their activity only and do not require any particular structure and comprise any combination of amino acid residues and/or mutations (including substitutions, deletions, additions) since the amino acid residues recited in the claims are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins. The recited genus of eukaryotic cells comprising the biomolecules having the activities and having no particular structure, comprises any prokaryotic, microorganism, eukaryotic or mammalian cell. As such, the described genera are biomolecules defined solely by their functional characteristics and any type of cell comprising said biomolecules defined solely by their functional characteristics, which is not sufficient characteristic for written description purposes. MPEP 2163.
However, the specification teaches specific mutant insect olfactory receptor proteins, including mutant Anopheles gambiae olfactory receptor 1 (AgOR1) proteins comprising SEQ ID NO: 3 and having substitutions M401L+K402S, M401L+K402N, or M401L+K402S+additional mutations (SEQ ID NOS: 45, 51 and 55).
The specification does not disclose any mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues.
Thereby, the specification has described in terms of its complete structure only the wild type polypeptide with activity and specific mutations therein (as discussed above).
The specification does not describe by other relevant identifying characteristics a representative number of additional species within the broadly claimed genus.
It is noted that the specification also teaches the general methodology for performing mutagenesis to obtain mutant insect olfactory receptor proteins and methods for measuring or detecting activity. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
This finding is also emphasized in Ex Parte Kubin (No. 2007-0819, Bd. Pat. Ann. & Int. May 31. 2007), wherein it is stated that:
“Although there is often significant overlap” between the enablement and written description requirements, “they are nonetheless independent of each other.” University of Rochester, 358 F.3d at 921, 69 USPQ2d at 1891. An “invention may be enabled even though it has not been described.” Id. Such is the situation here. While we conclude one skilled in the art would have been able to make and use the full scope of claim 73 through routine experimentation, we find Appellants did not describe the invention of claim 73 sufficiently to show they had possession of the claimed genus of nucleic acids. See, e.g., Noelle v. Lederman, 355 F.3d 1343, 1348, 69 USPQ2d 1508, 1513 (Fed. Cir. 2004) (“invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed”).
Thereby, a showing of how to potentially identify and make other nucleic acids/polypeptides is not sufficient to establish that Applicants were in possession of the invention as broadly claimed.
The skilled artisan cannot necessarily envision the detailed structures of ALL variants of any insect olfactory receptor protein comprising any amino acid sequence representative of formula 1 of unknown amino acid residues and having at least one condition selected from the group consisting of the conditions (1) to (3) because the specification provides minimal guidance as to which substitutions and/or deletions and/or additions and which amino acids are essential and critical for which insect olfactory receptor protein to have a changed property or activity, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the methods of making the claimed invention. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating or making it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Claims 1-11 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 mutant AgOR1 proteins comprising the amino acid sequence of SEQ ID NO: 45, 51 or 55, does not reasonably provide enablement for any and all mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues and having at least one condition selected from the group consisting of the conditions (1) to (3). 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 scope of the instant claims is not commensurate with the enablement of the instant disclosure, because practice of the claimed invention would require undue experimentation by an artisan of ordinary skill in the art to ascertain which mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues will have at least one condition selected from the group consisting of the conditions (1) to (3), and in which cells. Claims 1-11 are drawn to a mutant-insect olfactory receptor protein, comprising amino acid sequence B composed of amino acid sequence A containing a mutation, wherein the amino acid sequence A is in a corresponding wild-type insect olfactory receptor protein and represented by formula (1): ɸ7X1X2Z1X3X4Z2Z3ɸ6Uɸ5ɸ4ɸ3ɸ2ɸ1X5X6 wherein X1 to X6 and Z1 to Z3 represent amino acids derived from the amino acid sequence of the wild-type insect olfactory receptor, ɸ1 represents a hydrophobic amino acid, ɸ2 to ɸ7 each independently represent an uncharged polar amino acid or a hydrophobic amino acid, and U represents an uncharged polar amino acid, and the mutant insect olfactory receptor satisfies at least one condition selected from the group consisting of the conditions (1) to (3), etc., nucleic acid molecules encoding the mutant-insect olfactory receptor protein, and a cell comprising the nucleic acid molecules.
Accordingly, the claims encompass a significantly large genus of mutant insect olfactory receptor proteins, nucleic molecules encoding the mutant insect olfactory receptor proteins, and cells comprising the nucleic acid molecules. The recited genus of mutant insect olfactory receptor proteins are defined through their activity only and do not require any particular structure and comprise any combination of amino acid residues and/or mutations (including substitutions, deletions, additions) since the amino acid residues recited in the claims are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins. Thus, there could be a myriad and/or countless number of variants wherein the mutant insect olfactory receptor protein may or may not exhibit activity and exhibit property changes. Therefore, for the instant claimed invention, it would require an undue burden of experimentation for a skilled artisan to determine exactly which variants have activity and exhibit property changes.
The 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). The court in Wands states: “'Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. ''Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
In the instant case, the quantity of experimentation would be large since there are myriad substitutions and/or deletions and/or insertions and/or additions and amino acid residues to choose from to obtain mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues exhibiting property changes and/or having at least one condition selected from the group consisting of the conditions (1) to (3). The amount of guidance in the specification is minimal as to which substitutions at which positions in a wildtype insect olfactory receptor protein, i.e. AgOR1 protein, are essential and critical for having at least one condition selected from the group consisting of the conditions (1) to (3). In particular, the specification teaches specific mutant insect olfactory receptor proteins, including mutant Anopheles gambiae olfactory receptor 1 (AgOR1) proteins comprising SEQ ID NO: 3 and having substitutions M401L+K402S, M401L+K402N, or M401L+K402S+additional mutations (SEQ ID NOS: 45, 51 and 55) (see working examples).
The specification does not disclose any mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues. The nature of the invention is such that many different polypeptides that are substantially similar to insect olfactory receptor proteins may or may not have activity exhibiting property changes and conditions. The state of the prior art is that even proteins that are highly similar to the wild-type protein are at times not fully active. The relative level of skill in this art is very high. The predictability as to what substantially similar protein will have which activity is zero. When the factors are considered in their entirety, the Wands analysis dictates a finding of undue experimentation and thus, the claims are not enabled.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that in the examples of the instant specification, it was found that olfactory receptors derived from multiple species of insects belonging to the superorder Endopterygota have a common sequence represented by formula 1 (Figs. 1-4). Applicants assert that in the examples, it was found that chemical responsiveness of the receptors can be improved by introducing specific mutations into the common sequence (formula 1).
Applicants’ remarks are not persuasive. As noted in the 112(a) rejections above, the specification teaches specific mutant insect olfactory receptor proteins, including mutant Anopheles gambiae olfactory receptor 1 (AgOR1) proteins comprising SEQ ID NO: 3 and having substitutions M401L+K402S, M401L+K402N, or M401L+K402S+additional mutations (SEQ ID NOS: 45, 51 and 55).
The specification does not disclose any mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues.
The recited genus of mutant insect olfactory receptor proteins are defined through their activity only and do not require any particular structure and comprise any combination of amino acid residues and/or mutations (including substitutions, deletions, additions) since the amino acid residues recited in the claims are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins (i.e. formula 1). The recited genus of eukaryotic cells comprising the biomolecules having the activities and having no particular structure, comprises any prokaryotic, microorganism, eukaryotic or mammalian cell. As such, the described genera are biomolecules defined solely by their functional characteristics and any type of cell comprising said biomolecules defined solely by their functional characteristics, which is not sufficient characteristic for written description purposes. MPEP 2163.
As also previously noted, the specification teaches the general methodology for performing mutagenesis to obtain mutant insect olfactory receptor proteins and methods for measuring or detecting activity, it is known. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
Further, the quantity of experimentation would be large since there are myriad substitutions and/or deletions and/or insertions and/or additions and amino acid residues to choose from to obtain mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues exhibiting property changes and/or having at least one condition selected from the group consisting of the conditions (1) to (3). The amount of guidance in the specification is minimal as to which substitutions at which positions in a wildtype insect olfactory receptor protein, i.e. AgOR1 protein, are essential and critical for having at least one condition selected from the group consisting of the conditions (1) to (3). In particular, the specification teaches specific mutant insect olfactory receptor proteins, including mutant Anopheles gambiae olfactory receptor 1 (AgOR1) proteins comprising SEQ ID NO: 3 and having substitutions M401L+K402S, M401L+K402N, or M401L+K402S+additional mutations (SEQ ID NOS: 45, 51 and 55) (see working examples).
The specification does not disclose any mutant insect olfactory receptor proteins comprising any amino acid sequence representative of formula 1 of unknown amino acid residues.
For at least these reasons, the 112(a) rejections are maintained.
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 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 1 and dependent claims are drawn to a mutant-insect olfactory receptor protein, comprising amino acid sequence B composed of amino acid sequence A containing a mutation, wherein the amino acid sequence A is in a corresponding wild-type insect olfactory receptor protein and represented by formula (1): ɸ7X1X2Z1X3X4Z2Z3ɸ6Uɸ5ɸ4ɸ3ɸ2ɸ1X5X6 wherein X1 to X6 and Z1 to Z3 represent amino acids derived from the amino acid sequence of the wild-type insect olfactory receptor, ɸ1 represents a hydrophobic amino acid, ɸ2 to ɸ7 each independently represent an uncharged polar amino acid or a hydrophobic amino acid, and U represents an uncharged polar amino acid, and the mutant insect olfactory receptor satisfies at least one condition selected from the group consisting of the conditions (1) to (3), etc., nucleic acid molecules encoding the mutant-insect olfactory receptor protein, and a cell comprising the nucleic acid molecules.
Claim 1 is generally confusing and it is not clear what features are being recited in the mutant insect olfactory receptor protein. It is not clear what amino acid sequence(s) are comprised in the mutant insect olfactory receptor protein and which amino acid residues form the amino acid sequence(s) in the mutant insect olfactory receptor protein because the amino acid residues recited in the claim are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins. Further, it is not clear how amino acid sequence A is different than amino acid B to meet the conditions (1) to (3). Further clarification and/or correction is requested. Therefore, as currently written, the mutant insect olfactory receptor protein can reasonably comprise any amino acid sequence of an insect olfactory receptor polypeptide.
Claims 2-7 are generally confusing for the reasons noted above for claim 1 because the amino acid residues recited in the claims are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins and it is not clear what the amino acid sequence(s) are. Further clarification and/or correction is requested.
Claim 8 is confusing because it is not clear what is meant by the amino acid sequence A is a sequence “present closer” to the C-terminus of the amino acid sequence of the wild-type insect olfactory receptor protein.
Claims 9-11 are included in this rejection because they are dependent on the above claim(s) and fail to cure its defects.
Reply: Applicants assert that instant claim 1 has been amended to recite that “the wild-type insect olfactory receptor protein is a wild-type olfactory receptor protein of an insect in the superorder Endopterygota.” Applicants assert that this addresses the office’s concerns and makes the claims clearer.
Applicants’ remarks are not persuasive because the amendment does not address any of the issues noted above regarding what features are being recited in the mutant insect olfactory receptor protein in instant claim 1 and its dependent claims.
The 112(b) rejections are maintained for the reasons noted above.
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.
Claims 1-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (WO 03020913; IDS 12.11.24, previously cited). Since it is not clear what amino acid sequences and/or residues are present in the mutant insect olfactory receptor protein, for prior art purposes, the mutant insect olfactory receptor protein can reasonably comprise any amino acid sequence of an insect olfactory receptor polypeptide.
Lee et al. teach various Anopheles gambiae odorant receptor proteins comprising amino acid sequences represented by instant formula (1) and having representative amino acid residues and therefore, meeting the conditions recited (at least p. 19-21, also Figs. 1, 3-4; instant claims 1-9).
Regarding instant claim 10, Lee et al. teach nucleic acid molecules encoding the Anopheles gambiae odorant receptor proteins (at least p. 21-32).
Regarding instant claim 11, Lee et al. teach a host cell comprising the nucleic acid molecules encoding the Anopheles gambiae odorant receptor proteins (at least p. 32-35).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that starting from the amino acid sequence information recited in the claims, it is possible to easily determine whether it is a wild-type sequence or a mutant sequence based on a known database of wildtype sequences.
Applicants’ remarks are not persuasive because as currently written, it is not clear what features are being recited in the mutant insect olfactory receptor protein of instant claim 1. It is not clear what amino acid sequence(s) are comprised in the mutant insect olfactory receptor protein and which amino acid residues form the amino acid sequence(s) in the mutant insect olfactory receptor protein because the amino acid residues recited in the claim are merely representative of an amino acid sequence of the mutant insect olfactory receptor proteins. In other words, there is no amino acid sequence having a defined sequence being recited.
Therefore, since it is not clear what amino acid sequences and/or residues are present in the mutant insect olfactory receptor protein, for prior art purposes, the mutant insect olfactory receptor protein can reasonably comprise any amino acid sequence of an insect olfactory receptor polypeptide.
Therefore, the 102(a)(1) rejection is maintained for the reasons noted above.
No claim is allowed.
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 Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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