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
Claims 1-4 presented on 7/29/2024 are pending.
Claims 1-4 are for examination.
Claim Rejections, 35 U.S.C 112(a)
The following is a quotation of 35 U.S.C. 112(a):
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 1-4 are rejected under 35 U.S.C. 112(a), 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.
The claims are directed to A protein,(a-1) comprising at least one of amino acid substitutions below in an amino acid sequence set forth in SEQ ID NO: 1or 2, and(a-2) having glucocerebrosidase activity: (1-1) a substitution of an amino acid at a position corresponding to position 26 of SEQ ID NO: 1 or 2 with leucine (F26L); (1-2) a substitution of an amino acid at a position corresponding to position 26 of SEQ ID NO: 1 or 2 with isoleucine (F26I); (1-3) a substitution of an amino acid at a position corresponding to position 126 of SEQ ID NO: 1 or 2 with threonine (C126T);(1-4) a substitution of an amino acid at a position corresponding to position 126 of SEQ ID NO: 1 or 2 with serine (C126S) and a substitution of an amino acid at a position corresponding to position 342 of SEQ ID NO: 1 or 2 with serine (C342S);(1-5) a substitution of an amino acid at a position corresponding to position 57 of SEQ ID NO: 1 or 2 with cysteine (Q57C); (1-6) a substitution of an amino acid at a position corresponding to position 60 of SEQ ID NO: 1 or 2 with cysteine (H60C); (1-7) a substitution of an amino acid at a position corresponding to position 63 of SEQ ID NO: 1 or 2 with cysteine (T63C); (1-8) a substitution of an amino acid at a position corresponding to position 143 of SEQ ID NO: 1 or 2 with cysteine (Q143C);(1-9) a substitution of an amino acid at a position corresponding to position 145 of SEQ ID NO: 1 or 2 with cysteine (H145C); (1-10) a substitution of an amino acid at a position corresponding to position 224 of SEQ ID NO: 1 or 2 with cysteine (K224C); (1-11) a substitution of an amino acid at a position corresponding to position 321 of SEQ ID NO: 1 or 2 with cysteine (K321C); and(1-12) a substitution of an amino acid at a position corresponding to position 126 of SEQ ID NO: 1 or 2 with serine (C126T) and a substitution of an amino acid at a position corresponding to position 342 of SEQ ID NO: 1 or 2 with serine (C342S).
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." In this case, in light of the specification, the examiner has broadly interpreted claim is directed to A protein,(a-1) comprising at least one of amino acid substitutions below in an amino acid sequence set forth in SEQ ID NO: 1or 2 to A protein which can be any fragment of SEQ ID NO: 1 or 2 ( which are 536 aa residue long) ,(a-1) comprising at least one of amino acid substitutions below in an amino acid sequence set forth in SEQ ID NO: 1or 2 which only a few substitutions (1-1) to (1-12) comprise any variant having glucocerebrosidase activity.
The Court of Appeals for the Federal Circuit has recently 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." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fires v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
In the instant case, there is no structure associated with function with regard to the members of genus polypeptide that comprises a genus in an amino acid sequence set forth in SEQ ID NO: 1or 2 to A protein which can be any fragment of SEQ ID NO: 1 or 2 ( which are 536 aa residue long) ,(a-1) comprising at least one of amino acid substitutions below in an amino acid sequence set forth in SEQ ID NO: 1or 2 which only a few substitutions (1-1) to (1-12) comprise any variant having glucocerebrosidase activity. The specification does not describe the structure for all the polypeptide variants comprises glucocerebrosidase activity. The genus of glucocerebrosidase variant which has at least a few residue defined in any fragment of SEQ ID NO: 1 or 2 comprise any variant having glucocerebrosidase activity required in the claimed invention is an extremely large structurally and functionally variable genus. An argument can be made that the recited genus of is adequately described by the disclosure of the structure of polypeptide of SEQ ID NO: 1-2 and one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. However, as described below, the art clearly teaches the "Practical Limits of Function Prediction":
A. Davos 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 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, and page 105).B. Wristlock 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 polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Kwiatkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a beta -ketoacyl synthase into a malonyl decarboxylase and completely eliminates beta-ketoacyl synthase activity. The art also teaches that functionally similar molecules have different structures; Kiselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of a few genes of the structure of polypeptide of SEQ ID NO: 1-2 having recited glucocerebrosidase activity has been provided by the applicants’, which would indicate that they had the possession of the claimed genus of polypeptides and the encoding polynucleotides. The claimed genera of polynucleotides have widely variable structures and associated functions. As it is discussed above, a minor changes in structure may result in changes affecting function, since, the specification provided no additional information (species/variant/mutant) correlating structure with function, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. 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). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Applicant is 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 Rejections - 35 USC § 102
(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) 3 and 4 is/are rejected under 35 U.S.C. 102 (a)(1)] as being anticipated by Liou et al. ( JBC 2006, 281(7) pp 4242-4253, IDS.
Liou et al. disclose variants of beta glucosidase involving residues 48- 122, result 2-fold increases activity and were obtained with the L264I and C126S mutation and also C248S mutations ( teach applicants claims 3-4, see Table-2) (see Abstract, Table 1-2, FIG 1-2).
Claim Rejections - 35 USC § 103
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 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Do et al. (WO 2012/064709, also published as US PAT 8962564, US20120344054A1.) in view of Liou et al. ( JBC 2006, 281(7) pp 4242-4253, IDS),
Do et al disclosed variant, recombinant ß-glucocerebrosidase proteins characterized as having increased stability relative to recombinant wild-type ß- glucocerebrosidase. Also teach variant, recombinant ß-glucocerebrosidase proteins characterized as retaining more catalytic activity relative to recombinant wild- type ß-glucocerebrosidase. Further described variant, recombinant ß- glucocerebrosidase proteins that can have amino acid variations at one or more of the following positions: 316, 317, 321 and 145 ( see abstract), teach H145L/F relative to Sequence of humane SEQ ID NO: 1.
But did not teach H145C mutations as taught by instant application..
Liou et al. disclose variants of beta glucosidase involving various residues mutations such as Y363C mutation stabilize the enzyme ( see Table 1).
Therefore It would have been obvious to one of ordinary skill in the art at the time of the present application is filed combine the teaching of Liou et al., Do et al to recombinant ß-glucocerebrosidase proteins characterized as having increased stability relative to recombinant wild-type ß- glucocerebrosidase that can have amino acid variations at one or more of the following positions including 145 ( see abstract), as Do et al teach H145L/F perform a H145C mutation because Liou et al., teach that a C mutation of residues stabilize the enzyme too.. Because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable. The rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element for another yields predictable to one of ordinary skill in the art. Example (B) MPEP 2143
The rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element for another yields predictable to one of ordinary skill in the art. Example (B) MPEP 2143
Conclusion
Claims 1-4 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MOHAMMAD Y MEAH whose telephone number is (571)272-1261. The examiner can normally be reached on monday-friday (8-7).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on 4089187584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MOHAMMAD Y MEAH/Examiner, Art Unit 1652
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