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 .
Detail Action
Claims 1- 62 submitted are pending for examination.
Applicants election on 4/30/26 without traverse invention of group I Claims 1-34 and 49-50 directed to process for preparing a compound of Formula (Al)
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or a salt thereof, wherein ring A is C5-7 cycloalkyl or 5-7 membered heterocycloalkyl, comprising: a) treating a compound of Formula (A4)
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or a salt thereof, wherein Z is a protecting group, with Akl, wherein Akl is an acylating reagent, in the presence of an enzyme to provide a mixture of a compound of Formula (A2) and a compound of Formula (A3);
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or salts thereof; wherein RBisC1-6 alkyl optionally substituted with COOH; and b) deprotecting the compound of Formula (A2), or a salt thereof, to provide a compound of Formula (Al), or a salt thereof of the election/restriction office action of 12/3025. Groups II-IV; Claims 35-48 and 51-62 are withdrawn belonging to Non-elected inventions..
Claims 1-34 and 49-50 are for examination.
Election is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/13/2024, 8/27/2024 and 11/20/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the IDS statement.
Claim Rejections
Claim Rejections: 35 USC § 112(b)
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.
Claim 11 ,12 and 15 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 11 is indefinite in recitation of,.” lipase enzyme derived from Candida antarctica.” because it is unclear exactly what type of lipase enzyme is because derive can comprise fragment, mutant or recombinant form with unknown structure . It should be obtained from Candida antarctica
Claim 12 is indefinite in recitation of,.” lipase B enzyme derived from Candida antarctica.” because it is unclear exactly what type of lipase B enzyme is because derive can comprise fragment, mutant or recombinant form with unknown structure . It should be obtained from Candida antarctica
. Claim 15 is indefinite in recitation of,.” between about 15 °C and about 20 °C” because it is unclear between about mean who much between,. is it between 15 °C and 20 °C or something undefined temperature in between 15 °C and 20 °C.
Correction is required.
Claim Rejections, 35 U.S.C 112(a)
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.
Claims 1-34 and 49-50 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.
The claims are directed to process for preparing a compound of Formula (Al)
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or a salt thereof, wherein ring A is C5-7 cycloalkyl or 5-7 membered heterocycloalkyl, comprising: a) treating a compound of Formula (A4)
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or a salt thereof, wherein Z is a protecting group, with Akl, wherein Akl is an acylating reagent, in the presence of an enzyme to provide a mixture of a compound of Formula (A2) and a compound of Formula (A3);
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or salts thereof; wherein RBisC1-6 alkyl optionally substituted with COOH; and b) deprotecting the compound of Formula (A2), or a salt thereof, to provide a compound of Formula (Al), or a salt thereof using an enzyme or a lipase derived from Candida antarctica ( claims 11-12).
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 the claims by reciting “process for preparing a compound of Formula (Al)
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or a salt thereof, wherein ring A is C5-7 cycloalkyl or 5-7 membered heterocycloalkyl, comprising: a) treating a compound of Formula (A4)
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or a salt thereof, wherein Z is a protecting group, with Akl, wherein Akl is an acylating reagent, in the presence of an enzyme to provide a mixture of a compound of Formula (A2) and a compound of Formula (A3);
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or salts thereof; wherein RBisC1-6 alkyl optionally substituted with COOH; and b) deprotecting the compound of Formula (A2), or a salt thereof, to provide a compound of Formula (Al), or a salt thereof using any enzyme having any structure from any source or lipase enzyme derived from Candida antarctica comprise fragment, mutant or recombinant form with unknown structure ( see 112(b) above) .
Therefore in light of the above interpretation the claims are broadly interpreted use of any enzyme having any structure from any source or lipase enzyme derived from Candida antarctica comprise fragment, mutant or recombinant form with unknown structure ( see 112(b) above).
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 Fiers 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 this case, there is no structure associated with function with regard to the use of members of the genus of enzyme having any structure from any source or lipase enzyme derived from Candida antarctica comprise fragment, mutant or recombinant form with unknown structure ( see 112(b) above) having specific activity of producing process for preparing a compound of Formula (Al)
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or a salt thereof, wherein ring A is C5-7 cycloalkyl or 5-7 membered heterocycloalkyl, comprising: a) treating a compound of Formula (A4)
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or a salt thereof, wherein Z is a protecting group, with Akl, wherein Akl is an acylating reagent, in the presence of an enzyme to provide a mixture of a compound of Formula (A2) and a compound of Formula (A3);
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or salts thereof; wherein RBisC1-6 alkyl optionally substituted with COOH; and b) deprotecting the compound of Formula (A2), or a salt thereof, to provide a compound of Formula (Al), or a salt thereof .
The genus of enzyme polypeptides and encoding polynucleotides having specified activity modified in the claimed invention is an extremely large structurally and functionally variable genus. An argument can be made that the recited genus of enzymes is adequately described by the disclosure of the structure of ChiralpakAD3 or some few others as disclosed in page 42-43 of the specification, and one could use structural homology to isolate those and the encoding polynucleotides of defined structure disclosed in the table of page 42-43.. However, the art clearly teaches there is a practical limits to predict function of a polypeptide based structural homology:
Arts (Lima et al. Molecular catalysis, 2019, 466, pp 75-105) shows even Candida antarctica has lipases with diverse activity. See FIGS 5-25.
Even lipase enzyme disclose by applicants specification pages 42-43 in table shows lipase from Candida antarctica has diverse activity as for example entry 1 from shows 21% conversion with only 6/6% ee entry 2 shows 49% conversion with 99% ee.,
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 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. 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 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); Witkowski 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; Kisselev 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 species; ChiralpakAD3 or some few others as disclosed in page 42-43 having specific activity, has been provided by the applicants’, which would indicate that they had the possession of the claimed genus of polypeptides. The claimed genera of polypeptides and the encoding 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, and 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.
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
Conclusion
Claims 1-34 and 49-50 are rejected and no claim is allowable.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Mohammad Meah whose telephone number is 571-272-
1261. The examiner can normally be reached on 8:30-5PM.
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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