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
1. Applicant’s election of Group I (claims 1-6) without traverse in the reply filed on 5/21/26 is acknowledged. Applicant also elected the species of SEQ ID NO: 9 without traverse.
2. Claims withdrawn:
Claims 7-18 including non-elected species are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
3. Priority
Receipt is acknowledged of papers (foreign priority filed 11/4/21) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
4. Written Description
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 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 1-6 of the instant application filed 5/21/26 are drawn to as following genus.
1. A variant polypeptide of a parent polypeptide, wherein the parent polypeptide comprises the amino acid sequence of SEQ ID NO: 1, and wherein the variant polypeptide comprises an amino acid sequence which, when aligned with the amino acid sequence of SEQ ID NO: 1, comprises an amino acid substitution of V202I and/or A203N and/or V333S and/or Y335M and/or D336G, the positions of said amino acids being defined with reference to the amino acid sequence of SEQ ID NO: 1.
2. The variant polypeptide according to claim 1, wherein the variant polypeptide comprises or consists of an amino acid sequence having equal to or more than 70%, and more preferably equal to or more than 75%, 80%, 85%, 90%, 95, 98%, or 99%, sequence identity with the amino acid sequence of SEQ ID NO: 1.
3. The variant polypeptide according to claim 1, wherein any further amino acid substitutions in the variant polypeptide as compared to the parent polypeptide of SEQ ID NO: 1, other than Y335M and/or D336G and/or V202I and/or A203N and/or V333S, are conservative amino acid substitutions.
4. The variant polypeptide according to claims 1, wherein the variant polypeptide is a polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO: 7 or SEQ ID NO:9 or an amino acid sequence having equal to or more than 70%, and more preferably equal to or more than 75%, 80%, 85%, 90%, 95, 98%, or 99%, sequence identity with the amino acid sequence of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO: 7 and/or SEQ ID NO: 9.
5. The variant polypeptide according to claim 1, wherein the variant polypeptide is a protein having glucoamylase activity.
6. The variant polypeptide according to claim 1, wherein the variant polypeptide is synthetic polypeptide.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“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." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“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 the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, 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 disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[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.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
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.
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
In the instant case, there is limited structure associated with function with regard to the members of genus of the variant polypeptide comprises an amino acid sequence which, when aligned with the amino acid sequence of SEQ ID NO: 1, comprises an amino acid substitution of V202I and/or A203N and/or V333S and/or Y335M and/or D336G, the positions of said amino acids being defined with reference to the amino acid sequence of SEQ ID NO: 1. There is no limit to the extent of homology involved wherein ‘an amino acid sequence’ could be of any homology or even a fragment of the sequence of SEQ ID NO: 1 and with no function associated with the variant.
No information, beyond the characterization of a few variant species; wherein “A variant polypeptide of a parent polypeptide, wherein the parent polypeptide comprises the amino acid sequence of SEQ ID NO: 1, and wherein the variant polypeptide comprises an amino acid sequence which, when aligned with the amino acid sequence of SEQ ID NO: 1 is at least 95% identical to the variant sequence of SEQ ID NO: 1 and has glucoamylase activity, and comprises amino acid substitution of V202I and/or A203N and/or V333S and/or Y335M and/or D336G, with reference to the amino acid sequence of SEQ ID NO: 1.
The genus of 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 polypeptides is adequately described by the disclosure of the structures of SEQ ID NO: 1, 3, 5, 7 & 9 with specific structures having the associated function/activity, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”:
(a) 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). 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). Applicants’ are respectfully directed to the problems associated EC Classification in the section “Transferring the EC Classification enzyme to Non-Enzyme Comparisons”; pages 101-102 and Fig. 2a)-b), highlighting the structural and functional heterogeneity based on EC Classification numbers; as the stereo-specificity, substrate-specificity and catalytic properties vary widely.
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) 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).
(c) 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 b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity.
As stated above, no information beyond the characterization of a few species of variant polypeptide comprising an amino acid sequence which, when aligned with the amino acid sequence of SEQ ID NO: 1 is at least 95% identical to the variant sequence of SEQ ID NO: 1 and has glucoamylase activity, and comprises amino acid substitution of V202I and/or A203N and/or V333S and/or Y335M and/or D336G, with reference to the amino acid sequence of SEQ ID NO: 1.has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides and the encoding polynucleotides. As the claimed genera of polypeptides having widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. 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.
5. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 5 & 6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2014/039773 A1 (NOVOZYMES AS [DK]; CRAIG JOYCE [US]) 13 March 2014 (2014-03-13).
The reference of WO 2014/039773 A1 teaches new variant of a parent glucoamylase, used in a starch conversion process, for producing syrup and/or a fermentation product, for producing ethanol, and in a brewing process for producing a beverage.
WO 2014/039773 A1 teaches (e.g. abstract; page 2, lines 5-30; claims 1-26; examples; sequences, especially sequence 2) a glucoamylase variant from Trametes cingulata having an amino acid sequence as set forth in SEQ ID NO: 2 which shares 63.2% identity with SEQ ID NO: 1
of the present application and which, when aligned with the amino acid sequence of SEQ ID NO: 1 of the present application, comprises the amino acid substitutions of V202I, A203N, V333S, Y335M and D336G (the positions of said amino acids being defined with reference to the amino acid sequence of SEQ ID NO: 1 of the present application). A recombinant yeast cell (e.g. Saccharomyces cerevisiae) expressing said variant, as well as the use of said recombinant cell for the production of ethanol, is also described in this document.
While the reference does not specifically teach the variants claimed and since there is no limit to the extent of homology involved wherein ‘an amino acid sequence’ could be of any homology or even a fragment of the sequence of SEQ ID NO: 1 and with no function associated with the variant.
CC PN WO2014039773-A1.
XX
CC PD 13-MAR-2014.
XX
CC PF 06-SEP-2013; 2013WO-US058427.
XX
PR 07-SEP-2012; 2012US-0698170P.
XX
CC PA (NOVO ) NOVOZYMES AS.
XX
CC PI Vind J, Friis EP, Poulsen TA, Skjot M, Hansen PK, Rasmussen FW;
CC PI Krogsgaard S, Coward-Kelly G, Ayabe K, Craig J;
PNG
media_image1.png
691
626
media_image1.png
Greyscale
(sequence alignment of Applicants’ SEQ ID NO: 1 and AC BBE22991 of WO 2014/039773 A1 is presented above.) The claimed variants V202I, A203N, V333S, Y335M and D336G match when aligned with WO2014039773-A1 sequence presented above.
6. IDS filed 4/25/24 is acknowledged. A signed copy of the IDS is provided with this Office Action.
7. Abstract
*This application does not contain an abstract of the disclosure as required by 37 CFR 1.72(b). An abstract on a separate sheet is required.
*The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words [in length since the space provided for the abstract on the computer tape by the printer is limited]. The form and legal phraseology often used in patent claims, such as "means" and "said", should be avoided in the abstract. The abstract should sufficiently describe the disclosure to assist readers in deciding whether there is a need for consulting the full patent text for details. MPEP 608.01(b).
Line 3 of the abstract recite legal phraseology “said” which must be deleted.
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
Prosecution Insights