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
Election/Restrictions
1. Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Group I, claim(s) 1-10, drawn to a mutated luciferase, a nucleic acid molecule encoding said luciferase, an expression vector, or a recombinant cell comprising said nucleic acid molecule, classified in group C12N 15/00, for example.
II. Group II, claim(s) 11, drawn to a method of producing a mutated luciferase, classified in group C12N 15/09, for example.
III. Group III, claim (s) 12-13, drawn to a method of detecting a nucleic acid using mutated luciferase, classified in group C12N 15/67, for example.
IV. Group IV, claim(s) 14, drawn to a nucleic acid sequencing kit comprising mutated luciferase, classified in group C12Q 1/6869, for example.
V. Group V, claim(s) 15-16, drawn to a method for detecting a content of an analyte, classified in group C12Q 1/6872, for example.
VI. Group, claim(s) 17-18, drawn to a method for screening a substrate, classified in group C12Q 1/68, for example.
The inventions are distinct, each from the other because of the following reasons:
Inventions of Groups I and II are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make another and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP § 806.05(f)). In the instant case, the nucleic acid encoding mutant luciferase protein of Group II can be used in a materially different process of using that product, such as a hybridization method.
Inventions of Groups I-II are patentably distinct from the inventions of Groups III-VI because invention of Group III requires detecting a nutant luciferase, Group IV directed to a kit which encompasses components other than mutated luciferase, Group V requires detecting an analyte or Group VI requires screening substrates not required by the inventions of Groups I-II. The art search of Groups I-II and Groups III-VI are not coextensive.
Inventions of Groups III is patentably distinct from the inventions of Groups IV-VI because invention of Group IV directed to a kit which encompasses components other than mutated luciferase, Group V requires detecting an analyte or Group VI requires screening substrates not required by the inventions of Group III. The art search of Group III and Groups IV-VI are not coextensive.
Inventions of Groups IV is patentably distinct from the inventions of Group V because invention of Group IV directed to a kit which encompasses components other than mutated luciferase, whereas invention of Group V requires detecting an analyte or Group VI requires screening substrates not required by the inventions of Group IV. The art search of Group IV and Groups V-VI are not coextensive.
Inventions of Groups V is patentably distinct from the inventions of Group VI because invention of Group V requires detecting an analyte whereas invention of Group VI requires screening substrates not required by the inventions of Group V. The art search of Group V and Groups VI are not coextensive.
The examiner has required restriction between product and process claims. Where applicant elects claims directed to the product, and a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, Applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to rejoinder.
Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Restriction for examination purposes as indicated is proper because all these inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention;
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144.
If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other invention.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
During a telephonic interview with Mr. George McGuire on August 26, 2026 a provisional election was made to prosecute the claims of Group I, Claims 1-10. Thus claims 11-17 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected inventions. Affirmation of this election must be made by applicant in replying to this Office action.
Accordingly, claims 1-10 are examined on merits in the present Office action.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Information Disclosure Statement
2. Initialed and dated copies of Applicant’s IDS form 1449 filed in the papers of 12/30/2024. 02/06/2026 and 6/30/2026 are attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
3. Claims 1 and 5 are objected to because of the following informalities:
In Claim 1, it is suggested to recite “non-naturally occurring” before “mutated luciferase” for the clarity of the claimed subject matter. Dependent claims should be amended accordingly to provide antecedent basis. Failing to do so may invoke rejection under 101.
In claim 1, source of signal peptide must be clearly stated. For example, it is suggested to recite that signal peptide is at its N-terminus and consisting of amino acid residues 1-17 of SEQ ID NO: 2. Failing to do so may invoke rejection under 112(b).
Claim 5, embodiment 23, recites “G mutation at site 101 is I,” which departs from the “[residue] at site [n] is mutated to [residue]” format used throughout the remainder of claim 5 and should be conformed for clarity and consistency.
Claim Rejections - 35 USC § 112
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.
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.
4. Claims 1, 3 and 6-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has recently clarified the application of the written description requirement. The court stated that a written description of an invention "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., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material." Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus." Id.
Finally, the court held:
A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Id.
See also MPEP Section 2163, page 174 of Chapter 2100 of the August 2005 version, column 1, bottom paragraph, where it is taught that
[T]he claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.
See also Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ 2d 1016 at 1021, (Fed. Cir. 1991) where it is taught that a gene is not reduced to practice until the inventor can define it by "its physical or chemical properties" (e.g. a DNA sequence).
Claims are broadly drawn to a mutated luciferase, having at least one of the following mutation sites based on the amino acid sequence as set forth in SEQ ID NO: 2: sites 98, 99, 100, and 101, and the mutated luciferase comprising or not comprising a signal peptide amino acid sequence, or having one or two of the following mutation sites based on the amino acid sequence as set forth in SEQ ID NO: 2: sites 98, 99, 100 and 101.
The breadth of Claims 1 and 3 and claims dependent thereon (except claims 2, 4 and 5) encompass any type of mutation(s) at sites 98-101 in the amino acid sequence of SEQ ID NO: 2. For example, Claim 1 encompasses at least one mutation at any of positions 98-101 without identifying the replacement amino acid or limiting the number of mutated positions. Likewise, Claim 3 limits the number of mutated positions to one or two but likewise does not identify the replacement amino acids.
Accordingly, claims 1 and 3 encompass substitutions other than those described and tested in the specification. Claim 1 also encompasses undisclosed combinations involving mutations at two, three, or all four identified positions.
Assuming replacement by any of the other 19 naturally occurring amino acids, claim 1 encompasses approximately 159,999 substitution patterns across positions 98-101. Claim 3 encompasses approximately 2,242 single- and double-substitution patterns. These genera are materially broader than the particular mutants described and tested in the specification.
The disclosure does not establish that every amino acid is tolerated at each of positions 98-101. It also does not establish that the result obtained from a tested substitution predicts the effect of a chemically or structurally different, untested substitution at the same position. The specification further does not establish that the effect of a substitution at one position predicts the effect of a substitution at another position. Nor does it demonstrate that substitutions that are individually compatible with luciferase activity will remain compatible when combined.
Amino-acid substitutions may affect protein folding, catalytic activity, substrate recognition, emission intensity, emission spectrum, stability, and expression. The tested substitutions therefore do not, without an applicable structure–function correlation, necessarily represent all other substitutions encompassed by claims 1 and 3.
The specification does not disclose a structural principle or structure–function relationship that would permit a skilled artisan to extrapolate from the tested mutants to every untested substitution and combination covered by claims 1 and 3. Identification of positions 98-101 as possible mutation sites shows where additional mutants could be made and tested, but it does not demonstrate possession of every possible mutant at those positions.
Claims 6-18 incorporate, directly or indirectly, the full mutant-luciferase genus of claim 1. Their additional limitations concerning signal-peptide status, encoding nucleic acids, expression vectors, recombinant cells, production methods, detection methods, sequencing methods, kits, substrates, analytes, and substrate screening do not restrict the mutant luciferase to the substitutions adequately described in the specification.
Disclosure of an amino-acid sequence may support nucleic acids encoding that particular sequence because the genetic code is known. It does not, however, supply the missing description of mutant-protein sequences that were not themselves adequately described.
Similarly, disclosure of applications for the tested mutants does not demonstrate possession of those applications when practiced with every unsupported mutant encompassed by claim 1. The additional limitations in claims 6–18 therefore do not cure the written-description deficiency.
One of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the disclosure fails to describe the common attributes that identify members of the genus, and because the genus is highly variant, cited mutations in claims 2, 4 and 5 are insufficient to describe the claimed genus.
Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Accordingly, there is lack of adequate description to inform a skilled artisan that applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/Vol.66, No. 4/Friday, January 5, 2001/Notices; p. 1099-1111.
Accordingly, the specification does not reasonably convey that the inventors possessed the full scope of the mutant-luciferase genera recited in claims 1 and 3, or the subject matter of claims 6-10 insofar as those claims incorporate the unsupported genus of claim 1, as of the filing date.
5. Claims 1-10 are rejected under 35 U.S.C. § 112(a), or pre-AIA 35 U.S.C. § 112, first paragraph, because the specification, while enabling for, and reasonably conveying possession of, the specific single- and double-residue substitutions expressly exemplified in the specification (substantially corresponding to the twenty-seven embodiments of claim 5), does not enable, and does not reasonably convey that the inventor(s) are enabled for the full scope of the claimed invention as presently claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
A. Scope of the rejected genus
Independent claim 1 is directed to a mutated luciferase “having at least one of the following mutation sites based on the amino acid sequence as set forth in SEQ ID NO: 2: sites 98, 99, 100, and 101,” without limitation as to (i) the identity of the substituting amino acid at each site (any of the nineteen non-wild-type residues at each position, in the broadest reasonable interpretation, since claim 1 does not incorporate the specific substituent lists of claim 2), or (ii) the number and combination of the recited sites that are simultaneously mutated (one, two, three, or all four, in any combination). Even confined to the substituent lists of dependent claims 2 and 4 (5–11 alternative residues per site), the claimed genus spans hundreds of individual variants and, when combinations of two or more mutated sites are considered, several thousand theoretical sequence variants. The specification, however, provides working, data-supported examples for only the twenty-seven specific single- and double-substitution embodiments enumerated in claim 5.
B. Wands factor analysis
The claimed invention is not supported by an enabling disclosure taking into account the Wands factors. In re Wands, 858/F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988). In re Wands lists a number of factors for determining whether or not undue experimentation would be required by one skilled in the art to make and/or use the invention. These factors are: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples of the invention, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claim.
(i) Breadth of the claims: Very broad — claim 1 encompasses a mutation at any one or more of four recited sites, unconstrained as to substituent identity or combination, reading on an enormous genus of sequence variants relative to the specific embodiments for which functional data is provided. Likewise, breadth of claim 3 encompasses a mutation at any one or two recited sites, unconstrained as to substituent identity or combination, reading on an enormous genus of sequence variants relative to the specific embodiments for which functional data is provided.
(ii) Nature of the invention/(iii) State of the prior art: The invention concerns engineering the catalytic/substrate-binding function of a small, secreted, disulfide-stabilized copepod luciferase. The art recognizes that the structural determinants of luminescent activity in this specific enzyme family are still incompletely understood at the mechanistic level (see literature cited below), such that rational prediction of the functional consequence of a given substitution, without empirical testing, is not reliably possible.
(iv) Level of ordinary skill: High (protein/molecular biology, enzymology), but even highly skilled artisans in this field cannot dispense with empirical assay of individual variants, as reflected in the directed-evolution and deep-mutational-scanning literature cited below, which exists precisely because such empirical screening — rather than prediction — remains necessary.
(v) Level of predictability in the art: Low. Protein engineering of catalytic/luminescent function is a recognized area of substantial unpredictability; the effect of a given substitution routinely depends on the identity of the substituting residue, its structural context, and its interaction with other substitutions (epistasis), rather than following a generalizable rule applicable across the whole genus claimed.
(Vi) Amount of direction/guidance in the specification: Limited to disclosure of the twenty-seven specific embodiments of claim 5; no structure-function rationale, computational model, or algorithm is disclosed that would allow prediction of the functional consequence of the many substitutions and combinations falling within claim 1 but outside claim 5.
(vii) Existence of working examples: Present only for the specific substitutions of claim 5; absent for the balance of the substituent lists of claims 2 and 4, and absent entirely for any embodiment combining three or four simultaneously mutated sites.
(Viii) Quantity of experimentation necessary: High — skilled artisans would need to individually construct and empirically assay each of the very large number of un-exemplified single substitutions and multi-site combinations encompassed by claim 1 to determine which retain luciferase activity, because (as shown below) activity cannot be reliably predicted for a given substitution or combination from the working examples alone.
C. Documented unpredictability in protein/enzyme mutagenesis generally:
The unpredictability of the functional consequences of amino acid substitution is well documented in the peer-reviewed, non-patent scientific literature: See for example, Bowie et al. (Science 247:1306–1310; 1990, see the entire article) who teach establishing, through systematic scanning mutagenesis, that tolerance to substitution is position- and residue-specific and must be determined empirically rather than predicted a priori. Also see Guo et al. (Proc. Natl. Acad. Sci. USA 101(25):9205–9210, 2004, see the entire article) who teach that a substantial fraction (the “x factor,” on the order of one-third) of random single amino-acid substitutions functionally inactivate a protein, and that this probability cannot be assigned without empirical mutagenesis and screening. The unpredictability is also corroborated specifically for the family of secreted, coelenterazine-dependent copepod luciferases at issue in the present application. See for example, Markova et al. (Photochemistry and Photobiology, 95(3):705-721, 2019, see the entire article), who teach that a multiply-mutated Gaussia luciferase variant (“Gluc4”), engineered specifically to improve glow-type luminescence kinetics, unexpectedly exhibited approximately 100-fold reduced overall bioluminescence activity relative to the wild-type enzyme, illustrating that even deliberate, rationally motivated mutagenesis in this specific enzyme family produces functional outcomes that are not reliably predictable in advance, including outcomes severely detrimental to activity.
In view of the documented, art-recognized unpredictability of the functional effects of amino acid substitution generally, and of mutagenesis within the specific family of secreted copepod luciferases to which the claimed invention pertains, together with the breadth of claim 1 relative to the narrow set of working examples provided (substantially limited to the embodiments of claim 5), one of ordinary skill in the art would be required to engage in undue experimentation — namely, the individual construction and empirical activity-testing of a very large number of un-exemplified single substitutions and multi-site combinations — to practice the full scope of claim 1. The specification likewise does not reasonably convey that the inventor(s) had possession of the full claimed genus, as opposed to the twenty-seven specifically exemplified embodiments. See Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (disclosure of a functionally defined genus, without disclosure of a correlation between structure and function across the genus or a representative number of species, does not satisfy the written description requirement). Applicant’s general assertions that “specification is enabled for each mutation” are not, standing alone, evidence sufficient to overcome this rejection; enablement is assessed from the specification and the knowledge of one of ordinary skill in the art, not from applicant’s unsupported representations. In re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993).
Claims 2-4 are separately noted: although narrower than claim 1, each still recites, per site, a list of five to eleven alternative substituent amino acids, several of which fall outside the specific embodiments of claim 5 for which working examples are provided. To the extent any listed substituent in claims 2 and 4 is not among the specifically exemplified embodiments of claim 5, the enablement concern identified above applies with correspondingly reduced, but not eliminated, force.
Claims 7-10, to the extent each depends from or otherwise incorporates “the mutated luciferase according to claim 1” (or a nucleic acid, vector, or cell encoding or carrying the same), inherit the enablement deficiencies identified above with respect to claim 1 and are rejected on that additional, independent basis.
Given the breadth of the claims, unpredictability of the art and lack of guidance of the specification, as discussed above, undue experimentation would be required by one skilled in the art to make and use the claimed invention commensurate in scope with the claims.
Claim Rejections - 35 USC § 103
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.
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 nonobviousness.
6. Claim(s) 1, 3 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Takenaka et al. (Gene, 528:201-205, 2013).
Takenaka et al. teach ancestral luciferases "aCopLuc43" and "CopLuc48" which have a consensus sequence based on a number of copoepod luciferase sequences (abstract and Figure 1). Takenaka et al. further teach that Luciferase "aCopLuc43" has the sequence AQGI at positions 98-101 as compared to SEQ ID NO:2 of the present application and "aCopLuc48" has the sequence GQGP at positions 98-101 as compared to SEQ ID NO:2 of the present application (Figure 1, wherein Pleuromamma xiphias luciferase of SEQ ID NO:2 of the present application is referred to as PxLuc1-8).
Takenaka et al. teach also teach several copepod luciferases which have a different amino acid at positions 98, 99, 100 and/or 101 as compared to SEQ ID NO:2 of the present application (Figure 1, wherein Pleuromamma xiphias luciferase of SEQ ID NO:2 of the present application is referred to as PxLuc1-8). For example, MaLuc2 has A at position 98, PaLuc2 has K at position 98, HmLuc1 has D at position 98 and V at position 99 and I at position 100, HtLuc1-2-2 has E at position 99, MaLuc1 has A at positions 100 and 101. The reference further teach increase in activity and substrate specificity by expressing, for example MaLuc1 and MaLuc2 (see Table 1 and Fig. 3).
Although said luciferases are consensus luciferases or wild type luciferases, they are nevertheless encompassed by claim 1 because the recitation "mutated" of claim 1 is considered to be a product-by-process feature, i.e. obtained by mutation. Claim 1 is directed to a luciferase per se, irrespective of the method by which it is produced.
Takenaka et al. teach also teach expression of said luciferases in HEK293 cells using expression vector (p. 202, left col., par. 3).
It would have been thus obvious and within the scope of an ordinary skill in the art prior to earliest filing date of the instantly claimed invention to incorporate mutations at positions 98, 99, 100 or 101 of instant SEQ ID NO: 2 with or without signal sequence for the purpose of increasing substrate specificity as asserted by Takenaka et al. teachings and thus arrive at the Applicant’s claimed invention with a reasonable expectation of success and without any surprising results.
Thus, the claimed invention as a whole is prima facie obvious over the teachings of the prior art.
Conclusion
7. Claims 1-10 are rejected.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VINOD KUMAR whose telephone number is (571)272-4445. The examiner can normally be reached on 8:30 am - 5.00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad A. Abraham can be reached on (571) 270-7058 The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VINOD KUMAR/ Primary Examiner, Art Unit 1663
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