Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Detailed Action
Applicants’ amendment of 08/11/2026 in electing group II claims 7-12 now added new claims 13-17 without traverse in response to the restriction requirement office action of 6/11/2026 is acknowledged and entered. Claims 1-6 of group I are canceled.
Claims 7- 17 are pending for examination.
Claim Rejections: 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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.
Written Description
Claims 7-17 are rejected under 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 7-17 are directed to encompass polynucleotide encoding having any ketoreductase polypeptide comprising any variant polypeptide having at least about 80% identity to SEQ ID NO: 168, having a few aa mutations including position 40 is arginine and said variant polypeptide has said specific ketoreductase activity.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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, reduction to drawings, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states 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.
In the instant case, there is no structure associated with function with regard to the members of the genus of polypeptides i. e. any variant polypeptide of any parent ketoreductase having at least about 80% identity to SEQ ID NO: 168, having a few aa mutations including position 40 arginine and said variant polypeptide has ketoreductase activity.
No information, beyond the characterization of a few species: variant of SEQ ID NO: 168 having 20% variations anywhere within the polypeptide and said variant showing specific functional properties such as improved stereometrics activity as compared to wild-type enzyme, has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides.
The genus of polynucleotide encoding polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polynucleotide, polypeptides is adequately described by the disclosure of the structure of a protein comprising the amino acid sequence of SEQ ID NO: 168 having ketoreductase activity, since one could use structural homology to isolate those polynucleotide encoding polypeptides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: I. Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
II. Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340, in IDS) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
III. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity.
As stated above, no information beyond the characterization of a few species: a ketoreductase of SEQ ID NO: 168. Furthermore, “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).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim rejection 35 USC 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claim(s) 7-17 is/are rejected under pre-AIA 35 U.S.C. 102(e) as being anticipated by Campopiano et al. ( US Pat 7883879 priority date 2007).
The applied reference has a common inventor with the instant application. Based upon the earlier effective U.S. filing date of the reference, it constitutes prior art under pre-AIA 35 U.S.C. 102(e). This rejection under pre-AIA 35 U.S.C. 102(e) might be overcome either by a showing under 37 CFR 1.132 that any invention disclosed but not claimed in the reference was derived from the inventor or joint inventors (i.e., the inventive entity) of this application and is thus not the invention “by another,” or if the same invention is not being claimed, by an appropriate showing under 37 CFR 1.131(a).
Campopiano et al. disclose a ketoreductase polypeptide has at least 80% sequence identity to SEQ ID NO:168, has an arginine at position 40, glycine at position 146, and a I at position 93 and S at position 94, G at position 203, T at position 196.
See sequence alignment below:
US-12-243-968-66
; Sequence 66, Application US/12243968
; Patent No. 7883879
; GENERAL INFORMATION
; APPLICANT: CAMPOPIANO, Onorato
; APPLICANT:MUNDORFF, Emily
; APPLICANT:BORUP, Birthe
; APPLICANT:VOLADRI, Rama
; TITLE OF INVENTION: KETOREDUCTASE POLYPEPTIDES FOR THE PRODUCTION OF AZETIDINONE
; FILE REFERENCE: 376247-022
; CURRENT APPLICATION NUMBER: US/12/243,968
; CURRENT FILING DATE: 2008-10-01
; PRIOR APPLICATION NUMBER: 60/976,555
; PRIOR FILING DATE: 2007-10-01
; NUMBER OF SEQ ID NOS: 87
; SEQ ID NO 66
; LENGTH: 252
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: variant of L. kefir
US-12-243-968-66
Query Match 90.4%; Score 1171; DB 4; Length 252;
Best Local Similarity 90.1%;
Matches 227; Conservative 10; Mismatches 15; Indels 0; Gaps 0;
Qy 1 MTNRLKSKVAIVTGGTQGIGLAIA DKFVEEGAKVVITGRRADVGEKAAKSIGGTDVIRFV 60
||:||| ||||||||| |||||||||||||||||||||||||||||||||||||||||||
Db 1 MTDRLKGKVAIVTGGTLGIGLAIA DKFVEEGAKVVITGRRADVGEKAAKSIGGTDVIRFV 60
Qy 61 QHDVSDEAGWTKLFDTTEEAFGPVTTVVNNAGISLPKSLEDTTTEEWHKLLSVNLDGVFF 120
||| ||||||||||||||||||||||||||||| : ||:|||||||| ||||||||||||
Db 61 QHDASDEAGWTKLFDTTEEAFGPVTTVVNNAGIGVVKSVEDTTTEEWRKLLSVNLDGVFF 120
Qy 121 GTRLGIRRMKNKGLGASIINMSSISGIVGDPMLGAYNASKGAVRIMSKSAALDCAVKDYD 180
||||||:||||||||||||||||| |:|||| |||||||||||||||||||||||:||||
Db 121 GTRLGIQRMKNKGLGASIINMSSIFGMVGDPTLGAYNASKGAVRIMSKSAALDCALKDYD 180
Qy 181 VRVNTVHPGAIKTPLTDKWPAGGEMISQRTKTPMGHIGEPNDVAWVCVYLASDESKFATG 240
||||||||| ||||| | | ||:||||||||||||||||:|||||||||||||||||
Db 181 VRVNTVHPGPIKTPLLDDWEGAEEMMSQRTKTPMGHIGEPNDIAWVCVYLASDESKFATG 240
Qy 241 SEFVVDGGYTAQ 252
:|||||||:|||
Db 241 AEFVVDGGWTAQ 252
Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-6 of US PAT12110512. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case at least claim 1 of the instant application are directed to polynucleotide encoding the non-naturally occurring ketoreductase polypeptide having ketoreductase activity, comprising an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 168, wherein the residue at position 40 is arqinine. Claims 1-6 of US PAT12110512 are directed to ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 168 having at position 40 is R. The specification of US PAT12110512 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims 1-6 of instant application are obvious over claims 1-6 of US PAT12110512.
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-6 of US PAT10995320. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case claims of the instant application are directed to at least claim 1 of the instant application are directed to polynucleotide encoding the non-naturally occurring ketoreductase polypeptide having ketoreductase activity, comprising an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 168, wherein the residue at position 40 is arqinine. The specification of US PAT10995320 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims 1-6 of instant application are obvious over claims 1-6 of US PAT10995320.
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5 of US PAT10544400. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case claims of the instant application are directed to polynucleotide encoding polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 168 whish is mutant variants of SEQ ID NO: 168. Claims 1-5 of US PAT10544400 are directed to ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 168. The specification of US PAT10544400 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims 7-17 of instant application are obvious over claims 1-5 of US PAT10544400.
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5 of US PAT10053673. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case claims of the instant application are directed to at least claim 1 of the instant application are directed to polynucleotide encoding the non-naturally occurring ketoreductase polypeptide having ketoreductase activity, comprising an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 168, wherein the residue at position 40 is arqinine. Claims 1-5 of US PAT10053673 are directed to ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 168. The specification of US PAT10053673 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims 1-6 of instant application are obvious over claims 1-5 of US PAT10053673.
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-23 of US PAT9644189. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case claims of the instant application are directed to at least claim 1 of the instant application are directed to polynucleotide encoding the non-naturally occurring ketoreductase polypeptide having ketoreductase activity, comprising an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 168, wherein the residue at position 40 is arqininewhish is mutant variants of SEQ ID NO: 2. Claims 1-23 of US PAT9644189 are directed to DNA encoding ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 2, host cell expressing said DNA and method of making the polypeptide. The specification of encoding ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 2 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims of instant application are obvious over US PAT9644189.
Claims 7-17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-10 of US PAT 9040262. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In this case claims of the instant to at least claim 1 of the instant application are directed to polynucleotide encoding the non-naturally occurring ketoreductase polypeptide having ketoreductase activity, comprising an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 168, wherein the residue at position 40 is arqinine whish is mutant variants of SEQ ID NO: 2. Claims 1-10 of US PAT 9040262 are directed to the method of use ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 2. The specification of US PAT 9040262 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims of instant application are obvious over US PAT 9040262.
In this case claims of the instant application are directed to polynucleotide encoding polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 168 whish is mutant variants of SEQ ID NO: 2. Claims 1-6 of US PAT 9388391 directed mutant ketoreductase polypeptide of SEQ ID NO: 2,. The specification teach ketoreductase polypeptide which is mutant ketoreductase polypeptide of SEQ ID NO: 2 discloses the following specific embodiment of the instant claims and they are within the scope of claims therein which support recited in the claims. It would have been obvious to one of ordinary skill in the art to select this specific embodiment of the genera of the process to practice the invention thereof. Therefore claims of instant application are obvious over US PAT 9388391.
Submission of TDs for all the US patents used in the above rejections will overcome the above ODP rejections.
Conclusion
Claims 7-17 are rejected. No claim is allowed.
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/MOHAMMAD Y MEAH/Examiner, Art Unit 1652
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