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
Applicant’s election of Group I, claims 1-9 in part and as sequences SEQ ID NOs: 66-71 and 122 without traverse in the reply filed on 09/21/2026 is acknowledged. Claims 1-11 are pending in this application; Group I, claims 1-9 in part and elected sequences SEQ ID NOs: 66-71 and 122 reading on the elected invention is now under consideration for examination; non-elected sequences in Group I and claims 10-11 of non-elected Group II are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e) is acknowledged. This application claims the benefit of priority under 35 U.S.C. 119(e) to the US Provisional application: 63/464,682 filed on 05/08/2023.
Claim Objections
Claims 4-5 are objected to, as said claims recite non-elected subject-matter/SEQ ID NOs.
Claim Rejections: 35 USC § 112(a)
The following is a quotation 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.
Written Description
I. Claims 1-9 are rejected under 35 U.S.C. (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 1-9 of the instant application as interpreted are directed to a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8).
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 a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8).
No information, beyond the characterization of specific compositions with defined structures i.e., Examples 1-3 (see ¶ [0203-0220]; pages 50-55 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed members of the genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8).
The genus of polypeptides comprising undefined and unlimited structures i.e., plasmids comprising a genus of encoding genes required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited a the characterization of specific compositions with defined structures i.e., Examples 1-3 (see ¶ [0203-0220]; pages 50-55 of specification), since one could use structural homology to isolate or identify those polypeptides with the desired activity 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).
(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 and the art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; 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. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. 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 specific compositions with defined structures i.e., Examples 1-3 (see ¶ [0203-0220]; pages 50-55 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8). As the claimed genera of polypeptides having widely variable structure and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant/homologs) 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 35 U.S.C. (a) or 35 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 1-9 are rejected under 35 U.S.C. (a) or 35 U.S.C. 112, first paragraph, because the specification is enabling for the characterization of specific compositions with defined structures i.e., Examples 1-3 (see ¶ [0203-0220]; pages 50-55 of specification). However, specification does not reasonably provide enablement for members of the genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (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 claim(s).
Claims 1-9 are so broad as to encompass: a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8). The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of recombinant polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to the characterization of specific compositions with defined structures i.e., Examples 1-3 (see ¶ [0203-0220]; pages 50-55 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8). The specification provides no guidance with regard to the making of variants and mutants or with regard to other uses as claimed in the instant claims. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to use the full scope of the polypeptides and the encoding polynucleotides encompassed by these claims.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122, as claimed in claims 1-9, because the specification does not establish: (A) a rational and predictable scheme for identifying an enzyme of undefined and unlimited structural features exhibiting desired activity and with an expectation of obtaining the desired biological function; (B) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptides; (C) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain (as in claims 1-3, 6-7 and 9; no specific structure is recited for transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain); and to a genus of polypeptides having 70% sequence identity to SEQ ID NOs: 66-71 and 122 (as in claims 4-5 and 8). The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections: 35 USC § 102 (AIA )
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.
I. Claims 1-3, 6 and 9 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) and as evidenced by Corbi et al., (Gene Therapy., 2000, Vol. 7: 1076-1083) and Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313).
Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) disclose fusion proteins comprising a transposase Sleeping Beauty and fused to heterologous DNA-binding domains of (i) “Jazz protein” and (ii) “E2C protein” (see Abstract; Fig. 1, page 1138; Fig. 2-3, page 1139; and entire document); evidentiary references: (i) Corbi et al., (Gene Therapy., 2000, Vol. 7: 1076-1083) disclose that “Jazz protein” binds to nine base pair GC-rich region (see Abstract; Fig. 6, page 1080; Materials and Methods, col. 1, page 1082; and entire document); and (ii) Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) disclose that “E2C protein” binds to GC-rich region (see Abstract; TABLE 1, page 1302; Fig. 3, page 1306; Fig. 4B, page 1307; Fig. 5, page 1308; and entire document).
Therefore, Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) and as evidenced by Corbi et al., (Gene Therapy., 2000, Vol. 7: 1076-1083) and Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) is deemed to anticipate claims 1-3, 6 and 9 as written and when given the broadest reasonable interpretation.
II. Claims 1-3, 6 and 9 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) and as evidenced by Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) and Giniger et al., Cell, 1985, Vol. 40: 767-774).
Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) disclose fusion proteins comprising a transposase Sleeping Beauty and fused to heterologous DNA-binding domains of (i) “E2C protein” and (ii) “Gal4 protein” (see Abstract; Fig. 1-2, page 5; Fig. 3D, page 6; Fig. 5E, page 9; and entire document); evidentiary references: (i) Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) disclose that “E2C protein” binds to GC-rich region (see Abstract; TABLE 1, page 1302; Fig. 3, page 1306; Fig. 4B, page 1307; Fig. 5, page 1308; and entire document); and (ii) Giniger et al., Cell, 1985, Vol. 40: 767-774) disclose that “Gal4 protein” binds to GC-rich region (see Abstract; col. 2, ¶ 1, page 768; Fig. 7, page 770; Fig. 9, page 771; col. 2, ¶ 3, page 771; and entire document).
Therefore, Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) and as evidenced by Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) and Giniger et al., Cell, 1985, Vol. 40: 767-774) is deemed to anticipate claims 1-3, 6 and 9 as written and when given the broadest reasonable interpretation.
Since the Office does not have the facilities for examining and comparing applicants’ recombinant polypeptide of the instant invention with recombinant polypeptide of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed recombinant polypeptide of the instant invention and the recombinant polypeptide of the prior art (i.e., that the recombinant polypeptide of the prior art does not possess the same material structural and functional characteristics of the recombinant polypeptide of the instant invention). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Claim Rejections: 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
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(a) 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 nonobviousness.
Claims 1-9 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) and as evidenced by Corbi et al., (Gene Therapy., 2000, Vol. 7: 1076-1083) and Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) or Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) and as evidenced by Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) and Giniger et al., Cell, 1985, Vol. 40: 767-774) (see rejection above under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2)) as applied to claims 1-3, 6 and 9, and further in view of Yeung et al., (US 7,368,538; disclose a G+C rich binding protein having 100% sequence identity to SEQ ID NO: 66 of the instant invention); Hood et al., (US 8,586,006; disclose proteins having 100% sequence identities to SEQ ID NOs: 67, 69 and 70 of the instant invention); Mintz et al., (US 7,745,391; disclose a protein having 100% sequence identity to SEQ ID NO: 68 of the instant invention); Matsuyama et al., (US 5,891,666; disclose a protein having 100% sequence identity to SEQ ID NO: 71 of the instant invention); and Zhang et al., (US 7,345,217, annotated as MADS transcription factor comprising tetramerization domain having 100% sequence identity to SEQ ID NO: 122 of the instant invention; see provided sequence alignments).
Regarding claims 1-3, 6 and 9, Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) disclose fusion proteins comprising a transposase Sleeping Beauty and fused to heterologous DNA-binding domains of (i) “Jazz protein” and (ii) “E2C protein” (see Abstract; Fig. 1, page 1138; Fig. 2-3, page 1139; and entire document); and Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) disclose fusion proteins comprising a transposase Sleeping Beauty and fused to heterologous DNA-binding domains of (i) “E2C protein” and (ii) “Gal4 protein”.
However, disclosures of Ivics et al., or Yant et al., is silent regarding said reference GC-rich DNA is a transcription factor or DNA binding region of a transcription factor with at least 70% sequence identity to SEQ ID NOs: 66-71 and SEQ ID NO: 122 (as in claims 4-5 and 7-8).
Regarding claims 4-5 and 7-8, Yeung et al., (US 7,368,538; disclose a G+C rich binding protein having 100% sequence identity to SEQ ID NO: 66 of the instant invention); Hood et al., (US 8,586,006 disclose proteins having 100% sequence identities to SEQ ID NOs: 67, 69 and 70 of the instant invention); Mintz et al., (US 7,745,391; disclose a protein having 100% sequence identity to SEQ ID NO: 68 of the instant invention); Matsuyama et al., (US 5,891,666; disclose a protein having 100% sequence identity to SEQ ID NO: 71 of the instant invention); and Zhang et al., (US 7,345,217, annotated as MADS transcription factor comprising tetramerization domain having 100% sequence identity to SEQ ID NO: 122 of the instant invention).
Therefore, using the indications of Ivics et al., or Yant et al., as a reference, it would have been easy for a person skilled in the art to use the encoding polynucleotides that encode polypeptides annotated as GC-rich binding polypeptides/transcription factors or fragments thereof of Yeung et al., (US 7,368,538; disclose a G+C rich binding protein having 100% sequence identity to SEQ ID NO: 66 of the instant invention); Hood et al., (US 8,586,006 disclose proteins having 100% sequence identities to SEQ ID NOs: 67, 69 and 70 of the instant invention); Mintz et al., (US 7,745,391; disclose a protein having 100% sequence identity to SEQ ID NO: 68 of the instant invention); Matsuyama et al., (US 5,891,666; disclose a protein having 100% sequence identity to SEQ ID NO: 71 of the instant invention); and Zhang et al., (US 7,345,217, annotated as MADS transcription factor comprising tetramerization domain having 100% sequence identity to SEQ ID NO: 122 of the instant invention; see provided sequence alignments) and generate a recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain. As such, disclosures of Yeung et al., Hood et al., Mintz et al., Matsuyama et al., and Zhang et al., provide the structural and functional elements in the claimed recombinant polypeptide comprising a transposase or fragment or a derivative thereof having transposase function and at least one heterologous GC Rich DNA Binding Domain (GRDBD) or at least one heterologous multimerization domain of interest depending on the experimental need.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claimed recombinant polypeptide, as suggested by the teachings of Yeung et al., Hood et al., Mintz et al., Matsuyama et al., and Zhang et al., and to modify the teachings of Ivics et al., or Yant et al. A person of ordinary skill in the art is motivated to make such change depending on the experimental need. One of ordinary skill in the art has a reasonable expectation of success to generate a fusion polypeptide comprising a transposase and GC-rich binding domain, and are well known in the art. Therefore, the invention as a whole lack an inventive step over the prior art. The expectation of success is high, because the combined teachings of Ivics et al., or Yant et al., Yeung et al., Hood et al., Mintz et al., Matsuyama et al., and Zhang et al., also provide the structural and functional elements of the instant invention (Teaching, Suggestion and Motivation).
Furthermore, "it is prima facie obvious to combine two compositions or two methods each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition or third method to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
Thus, given that the cited the prior art provides scientific basis and reduction to practice of claimed fusion polypeptide comprising a transposase and GC-rich binding domain, examiner takes the position that the claimed fusion polypeptide comprising a transposase and GC-rich binding domain as claimed herein in claims 1-9, is a simple combination of known elements from the prior art.
THE EXPECTATION OF SOME ADVANTAGE IS THE STRONGEST RATIONALE FOR COMBINING REFERENCES
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, scientific principles or legal precedent, that some advantage or expected beneficial result would 217USPQ 1, 5-6 (Fed. Cir. 1983). >See also Dystar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick, 464 F.3d 1356, 1368, 80 USPQ2d 1641, 1651(Fed. Cir. 2006) (“Indeed, we have repeatedly held that an implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal-and even common-sensical-we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves.”).
The cited references render claims 1-9 prima facie obvious to one of ordinary skill in the art when one applies the Teaching, Suggestion and Motivation (TSM) test under the rationale for arriving at a conclusion of obviousness as suggested by the KSR ruling. The rationale applied for this rejection is as follows:
(1) Combining prior art elements according to known method to yield predictable results.
(2) Simple substitution of one known element for another to obtain predictable results.
(3) "Obvious to try"- choosing from a finite number of identified, predictable solution, with a reasonable expectation of success.
Therefore, claims 1-9 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ivics et al., (Mol. Therapy., 2007, Vol. 15(6): 1137-1144) and as evidenced by Corbi et al., (Gene Therapy., 2000, Vol. 7: 1076-1083) and Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) or Yant et al., (Nuc. Acids Res., 2007, Vol. 35(7), e50: pages 1-13) and as evidenced by Tan et al., (J. Virol., 2004, Vol. 78(3): 1301-1313) and Giniger et al., Cell, 1985, Vol. 40: 767-774) (see rejection above under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2)) as applied to claims 1-3, 6 and 9 and further in view of Yeung et al., (US 7,368,538; disclose a G+C rich binding protein having 100% sequence identity to SEQ ID NO: 66 of the instant invention); Hood et al., (US 8,586,006 disclose proteins having 100% sequence identities to SEQ ID NOs: 67, 69 and 70 of the instant invention); Mintz et al., (US 7,745,391; disclose a protein having 100% sequence identity to SEQ ID NO: 68 of the instant invention); Matsuyama et al., (US 5,891,666; disclose a protein having 100% sequence identity to SEQ ID NO: 71 of the instant invention); and Zhang et al., (US 7,345,217, annotated as MADS transcription factor comprising tetramerization domain having 100% sequence identity to SEQ ID NO: 122 of the instant invention; see provided sequence alignments).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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