DETAILED ACTION
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 .
1. Formal Matters
A. In the response filed 6/3/26, Applicants elected Group I without traverse. Therefore, this restriction is deemed proper and is made FINAL.
B. Claims 43-72 are pending. Claims 54-68 are withdrawn as being drawn to a non-elected invention. Claims 43-53 and 69-72 are the subject of this Office Action.
2. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors, embedded hyperlinks, or improperly referenced trademarks. Applicants’ cooperation is requested in correcting any errors of which Applicants may become aware.
3. Claim Objections
A. Claims 43, 45, 46, 51-53 and 72 are objected to since “recombinantly produced” should not be hyphenated.
B. Claim 48 is objected to since “polyhistidine” should be one word.
C. Claim 53 is objected to since, in part (a), there is an extra space between “to” and “about”.
D. It is suggested that claim 53(c) be amended to “between 0”.
E. Claims 69 recites both SEQ ID NO:2 and 7. It is believed that only SEQ ID NO:7 should be recited.
4. Claim Rejections - 35 USC § 112(a) – scope of enablement
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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 43-53 and 69-72 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the ligase of SEQ ID NO:1 fused to an HU protein, does not reasonably provide enablement for (1) any other ATCV-1 ligase, nor for (2) “functional variants” of HU proteins. 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 the invention commensurate in scope with these claims.
In In re Wands, 8USPQ2d, 1400 (CAFC 1988) page 1404, the factors to be considered in determining whether a disclosure would require undue experimentation include (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 claims.
The breadth of the claims is excessive with regard to claiming (1) all ATCV-1 ligases (2) fused to all functional variants of an HU protein. The specification defines HU proteins as –
small, basic, heat-stable DNA-binding protein that are well-conserved in prokaryotes and associated with the bacterial nucleoid. Examples of HU proteins include, without limitation, the following: UniProtKB Entries P0ACF0 (DBHA_ECOLI) (Escherichia coli), P0ACF0 (DBHA_ECOLI) (Escherichia coli), P0ACF4 (DBHB_ECOLI) (Escherichia coli), EOJ6W8 (DBHA_ECOLW) (Escherichia coli), P0ACF2 (DBHA_ECO57) (Escherichia coli), P0ACF1 (DBHA_ECOL6) (Escherichia coli), POA3H0 (DBH_GEOSE) (Geobacillus stearothermophilus (Bacillus stearothermophilus)), P05514 (DBH_NOSS1) (Nostoc sp.), P52680 (DBHA_SERMA) (Serratia marcescens), P52681 (DBHB_SERMA) (Serratia marcescens), P0ACF3 (DBHA_SHIFL) (Shigellaflexneri), Q31TZ7 (Q31TZ7_SHIBS) (Shigella boydii), and AOA2T4HNA2 (AOA2T4HNA2_MORMO) (Morganella morganii (Proteus morganii)).
First, regarding ATCV-1 ligases, the specification and claims only provide guidance and working examples of SEQ ID NO:1 (e.g. Examples 8 and 10). While it is possible that SEQ ID NO:1 is the only ligase in ATCV, though support is requested if this argument is relied upon, the issue still remains regarding claim 44, which recites “at least 90% identical to SEQ ID NO:1”. These proteins, obviously, would have one or more amino acid substitutions, deletions, insertions and/or additions to the protein of SEQ ID NO:1 and Applicants do not provide any guidance or working examples of critical residues that would be required to maintain the function of the ligase. Given that the ligase is 300 residues, this would mean that up to 30 could be altered. Given this lack of guidance and working examples, it is not predictable to one of ordinary skill in the art how to make a functional ligase other than SEQ ID NO:1.
In addition, the claims are drawn to any “functional variant” of any HU protein. However, similar to that discussed above regarding ligase, there is no limitation to the number of changes that could be made to the HU protein, especially in the absence of a definition of “functional variant”, as no specific function is defined. “Acting as an antigen” can, respectfully, be considered a function. Regardless, the term allows for every amino acid residue in any known HU protein to be altered and, again, neither the specification nor the claims provide any guidance or working examples of any changes or variant. It is noted that the definition of HU proteins includes the phrase “without limitation”; however, though this could encompass countless variants, it appears that the phrase is referring to all known HU proteins without limiting themselves to those exemplified. Therefore, no issue is being raised if this is, in fact, the case.
Again, given this lack of guidance and working examples, it is not predictable to one of ordinary skill in the art how to make a functional variant of any known HU protein.
Finally, claim 52 recites that the ligase is thermostable at a temperature above at least 16oC and claim 53 recites ligation efficiency under various conditions. However, while these do provide functional limitations, Applicants have not provided any guidance or working examples of any ligase other than SEQ ID NO which would meet at least some of the limitations, though it is unclear which. Furthermore, it is noted that claim 52 does not recite an upper limit to temperature). Regardless, the specification does not provide any guidance or working examples of any variant, including those at least 90% identical to SEQ ID NO:1, which meet the limitations of claims 52 and 53, including, but not limited to, a stability at a temperature with no upper limit.
These factors lead the Examiner to hold that undue experimentation is necessary to practice the invention as claimed.
5. Claim Rejections - 35 USC § 112(a) – written description
Claims 43-53 and 69-72 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.
These are genus claims. Other than (1) being an ATCV-1 ligase and (2) a functional HU variant, the specification and claims do not indicate what distinguishing attributes are shared by the members of the genus. Thus, the scope of the claims includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between/among genus members is permitted. The specification and claims do not provide any guidance as to what changes should be made. Structural features that could distinguish compounds in the genus from others in the nucleic acid or protein class are missing from the disclosure. No common structural attributes identify the members of the genus.
The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, SEQ ID NO:1, and the wild-type HU proteins recited in the specification, alone, are insufficient to describe the genus. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus. Thus, Applicant was not in possession of the claimed genus at the time the invention was made.
Regarding claims 52 and 53, claim 52 recites that the ligase is thermostable at a temperature above at least 16oC and claim 53 recites ligation efficiency under various conditions. However, while these do provide functional limitations, Applicants have not provided written description of any ligase other than SEQ ID NO which would meet at least some of the limitations, though it is unclear which. Furthermore, it is noted that claim 52 does not recite an upper limit to temperature. Regardless, the specification does not provide written description of any variant, including those at least 90% identical to SEQ ID NO:1, which meet the limitations of claims 52 and 53, including, but not limited to, a stability at a temperature with no upper limit.
6. Prior Art of Interest Not Relied Upon
A. U.S. Patent No. 10,640,812 teaches instant SEQ ID NO:1, but does not teach, nor can the Examiner make a prima facie case for, fusing the ligase to an HU protein.
Patent No. 10640812
GENERAL INFORMATION
APPLICANT: GlaxoSmithKline Intellectual Property Development Limited
APPLICANT: CRAMERI, Andreas,et al.
APPLICANT: HILL, Malcolm Leithhead
TITLE OF INVENTION: NOVEL PROCESSES FOR THE PRODUCTION OF OLIGONUCLEOTIDES
FILE REFERENCE: PB66127T
CURRENT APPLICATION NUMBER: US/15/643,535
CURRENT FILING DATE: 2017-07-07
PRIOR APPLICATION NUMBER: GB 1612011.5
PRIOR FILING DATE: 2016-07-11
NUMBER OF SEQ ID NOS: 62
SEQ ID NO 54
LENGTH: 300
TYPE: PRT
ORGANISM: Acanthocystis turfacea Chlorella virus TN603.4.2
Query Match 100.0%; Score 1561; Length 300;
Best Local Similarity 100.0%;
Matches 300; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAIQKPLLAASLKKMSVDNLTFPVYATPKLDGIRALKIDGTLVSRTFKPIRNTTISKVLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAIQKPLLAASLKKMSVDNLTFPVYATPKLDGIRALKIDGTLVSRTFKPIRNTTISKVLA 60
Qy 61 SLLPDGSDGEILSGKTFQDSTSTVMTTDAGIGSDTTFFWFDYVKDDPDKGYLDRIADMKT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SLLPDGSDGEILSGKTFQDSTSTVMTTDAGIGSDTTFFWFDYVKDDPDKGYLDRIADMKT 120
Qy 121 FVDQHPEILKDSCVTIVPLFPKKIDTPEELHVFEKWCLDQGFEGVMVRTAGGKYKFGRST 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FVDQHPEILKDSCVTIVPLFPKKIDTPEELHVFEKWCLDQGFEGVMVRTAGGKYKFGRST 180
Qy 181 EKEQILVKIKQFEDDEAVVIGVSALQTNTNDKKLNQLGEMRRTSHQDGKVDLDMLGALDV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 EKEQILVKIKQFEDDEAVVIGVSALQTNTNDKKLNQLGEMRRTSHQDGKVDLDMLGALDV 240
Qy 241 DWNGIRFSIGTGFDKDTREDLWKQRDSIVGKVVKFKYFSQGIKTAPRFPVFLGFRDENDM 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 DWNGIRFSIGTGFDKDTREDLWKQRDSIVGKVVKFKYFSQGIKTAPRFPVFLGFRDENDM 300
B. Regarding claim 69, Boehm et al. (U.S. Patent No. 7,435,595) teaches the HU protein of instant SEQ ID NO:7.
Patent No. 7435595
GENERAL INFORMATION
APPLICANT: Boehm, Gerald
APPLICANT: Esser, Dirk
APPLICANT: ACGT ProGenomics AG
TITLE OF INVENTION: Method for Transfer of Molecular Substances With
TITLE OF INVENTION: Prokaryotic Nucleic Acid-Binding Proteins
FILE REFERENCE: 080375-000000US
CURRENT APPLICATION NUMBER: US/10/954,549A
CURRENT FILING DATE: 2004-09-29
PRIOR APPLICATION NUMBER: US/10/129,393
PRIOR FILING DATE: 2002-10-28
PRIOR APPLICATION NUMBER: DE 199 52 983.3
PRIOR FILING DATE: 1999-11-03
PRIOR APPLICATION NUMBER: WO PCT/EP00/10875
PRIOR FILING DATE: 2000-11-03
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 7
LENGTH: 90
TYPE: PRT
ORGANISM: Escherichia coli
FEATURE:
OTHER INFORMATION: HU DNA-binding protein, alpha subunit, GenBank
GI:118256
Query Match 100.0%; Score 435; Length 90;
Best Local Similarity 100.0%;
Matches 90; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNKTQLIDVIAEKAELSKTQAKAALESTLAAITESLKEGDAVQLVGFGTFKVNHRAERTG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNKTQLIDVIAEKAELSKTQAKAALESTLAAITESLKEGDAVQLVGFGTFKVNHRAERTG 60
Qy 61 RNPQTGKEIKIAAANVPAFVSGKALKDAVK 90
||||||||||||||||||||||||||||||
Db 61 RNPQTGKEIKIAAANVPAFVSGKALKDAVK 90
7. Conclusion
A. No claim is allowable.
B. SEQ ID NO:8 and 9 are free of the prior art.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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