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 .
Election/Restrictions
In response to the species election, Applicant elected SEQ ID NO:2607 from Table 3A, SEQ ID NO:329 as the LeftRegion and SEQ ID NO:235 of the RightRegion without traverse on 11/5/2025. All other sequences are withdrawn from consideration at this time.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 64, line 4. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show color discernment as described in the specification. Page 58, lines 27-28 recite, “a core that is common between the attP and attB site, indicated here by gray shading”. However, the gray shading does not appear to be present in figure 5A. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 1-5 and 11-20 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.
When determining if a recited genus has adequate written description for a genus:
(1) the broadest reasonable interpretation of the genus is determined;
(2) the disclosure is examined to determine if the specification has provided a representative number of species to describe the complete structure of the genus;
(3) the disclosure is examined to determine whether a representative number of species have been sufficiently described by other relevant characteristics, specified features and functional attributes that would distinguish different members of the claimed genus; and
(4) the state of the art is examined to the determine if it supports/supplement the genus description in the specification in a manner that would demonstrate the application was in possession of the claimed genus at the time of effectively filing.
Breadth of the Genus Claimed:
Claims 1 and 2 recite “an amino acid sequence having at least 70% identity thereto”. “An” amino acid sequence indicates that amino acid fragments, variants in sequence in length, and the full length sequence meet the limitations of the recitation. Having at least 70% thereto means that at least 70% of amino acid residues must be conserved and 30% of them can be altered by deletion, addition, or substitution. The 30% amino acids residues that can be changed can be contiguous or non-contiguous. The recited amino acid sequences are in reference to tens of thousands of SEQ ID NOS present in Tables 3A-C. As such, the number of possible species comprised in the genus of “an amino acid sequence having at least 70% identity thereto” is unimaginably large with a large number of divergent amino acid sequence species.
Claims 1 and 3 recites, “a nucleic acid sequence having 70% identity to said parapalindromic region or having no more than 20 sequence alterations relative thereto”. “A” nucleic acid sequence indicates that nucleotide fragments, variants in sequence in length, and the full length sequence meet the limitations of the recitation. Having at least 70% thereto means that at least 70% of nucleotides must be conserved and 30% of them can be altered by deletion, addition, or substitution. The 30% nucleotides that can be changed can be contiguous or non-contiguous. The recited nucleic acid sequences are in reference to tens of thousands of SEQ ID NOS present in Tables 3A-C. As such, the number of possible species comprised in the genus of “an nucleic acid sequence having at least 70% identity thereto” is unimaginably large with a large number of divergent amino acid sequence species. Similarly “having no more than 20 sequence alterations” encompasses any unit of substitution, deletion, addition of one or more nucleotides. One “sequence alteration” can be to alter remove any number of nucleotides at once or make a point mutation. As such, the number of species in this genus is an unimaginable number of divergent sequences species.
Specification Description:
The specification recites an extremely large number of SEQ ID NOS: in Tables 3A-3C. All of the SEQ ID NOS: encode serine recombinases isolated of different phage variants. The specification does not describe any species examples of each of the SEQ ID NO that have at least 70% identity. As such, these tables solely disclose sequences with 100% identity to full length SEQ ID NOS.
The specification recites an extremely large number of SEQ ID NOS: in Tables 2A-2C. All of the SEQ ID NOS: encode parapalindromic sequences recognized by the serine recombinases of tables 3A-C. The specification does not describe any species examples of each of the SEQ ID NO that have at least 70% identity. As such, these tables solely disclose sequences with 100% identity to full length SEQ ID NOS.
The specification teaches that sequence alterations in Tables 2A-C encompass substitutions, insertions, or deletions (see [006] of the pregrant publication). The specification teaches that sequence alterations in Tables 3A-C encompass substitutions, insertions, or deletions (see [0007] of the pregrant publication). The specification does not describe any regions within the SEQ ID NOS that can be altered in any ways an retain intact recombinase or parapalindromic sequence function.
State of the Art:
While means of make alterations in amino acid sequences or nucleic acid sequences have long been established in the prior art using recombinant technology, the ultimate impact of such alterations on sequences binding, sequence function, sequence secondary and/or tertiary structure is unpredictable (see for example, Berkman printout from https://www.genome.gov/genetics-glossary/Substitution#. 2025, pages 1-4).
In conclusion, the genus “an amino acid sequence having at least 70% identity thereto” and the genus “a nucleic acid sequence having 70% identity to said parapalindromic region or having no more than 20 sequence alterations relative thereto” lack adequate written description. Both the amino acid sequence genus and the nucleic acid sequence genus comprise an unimaginable number of different species sequences and the specification solely describe the full length sequences for all the SEQ ID NOS listed in Tables 2A-C and Tables 3A-C. A disclosure of the full length sequences solely provide a small subpopulation of the possible sequences of both these genuses. Further the specification fails to describe any regions in these sequences that can be altered and still maintain function as required by the invention. As such, the specification fails to describe a representative number of species to teach the complete structure of the amino acid sequence genus claimed and the nucleic acid sequence genus claimed. Further, the art teaches that altering sequences can change their function in unpredictable ways. As such, the skill artisan would not be able to envision the complete structure of the two genuses claimed and thus would conclude that the application was not in possession of the complete genuses claimed at the time of effective filing.
Claim Rejections - 35 USC § 112
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.
Claims 1-20 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.
Claims 1-3 recite, “Tables 2A, 2B, or 2C” and/or “Tables 3A, 3B, or 3C”.
MPEP § 2173.05(s) states, “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parteFressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
All of the SEQ ID NOS disclosed in these table can be written out in claims. As such, incorporation by reference is not permitted.
Claims 1 and 3 recites the terms “LeftRegion” and “RightRegion”. It appears that these are terms being designated by Applicant. While Applicant is allowed to be their own lexicographer, a clear definition or delineate of the feature which these refers stand is not apparent from the specification. As such, the metes and bound of these terms are not apparent.
The remainder of the claims are dependent upon claims 1-3 and thus also comprise the above discussed Tables.
Claim 1 and 2 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of an amino acid sequence of Tables 3A-C is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: These above tables disclose amino acid sequences for a large number of SEQ ID NOS, each having a different primary sequence and having unique corresponding DNA recognition sequences. As such, each SEQ ID NO represents a structurally different recombinase that functions binding to structurally different elements.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claims 1 and 3 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of a nucleic acid sequence of Tables 2A-C is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: These above tables disclose nucleic acid sequences for a large number of SEQ ID NOS, each having a different primary sequence and recognize different recombinase variants. As such, each SEQ ID NO represents a structurally different DNA recognition sequences LeftRegions or RightRegions that functions binding to structurally different elements.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claim 1 provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 11 of copending Application No. 18563127 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Regarding instant claim 1, Copending claim 11 discloses a system for modifying DNA comprising: (a) recombinase polypeptide comprising an amino acid sequence of any one of SEQ ID NOS:1-1143 (i.e. tables 3A, 3B, or 3C) or an amino acid sequence having at least 70% identity thereto; b) a double stranded insert DNA comprising: i) a DNA recognition sequence that binds to the recombinase polypeptide of a) having the recognition sequences set forth within SEQ ID NOS:13,001-25677 or SEQ ID NO:26001-38677 (i.e. SEQ ID NOS of tables 2A-C) or 70% identical to; and ii) a heterologous object sequence. SEQ ID NO:329 of the instant application has 100% identity to SEQ ID NO:24803 of the copending application. SEQ ID NO:1235 has 100% identity to SEQ ID NO:37803 of the copending application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 2-5, 11-12, 14-17, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 22 of copending Application No. 18563127 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 2-20 are obvious variants of the copending claims 11 and 22.
Regarding claim 2-3, copending claim 11 teaches the claimed system for modification of DNA as discussed above. However, copending claim 11 does not teach that the system is present in a eukaryotic cell. However, the recited intended use is for modifying a DNA and DNA are comprised in eukaryotic and prokaryotic cells. As such, it would have been obvious to modify the DNA with the claimed system of copending claim 11 in a finite number of possible cells, chosen from eukaryotic or prokaryotic cell as claimed to predictably arrive at the limitations of instant claims 2-3.
Regarding claims 4-5, copending claim 22 directed to a cell comprising a first parapalindromic sequence of SEQ ID NOS:13,001-25677 or SEQ ID NO:26001-38677 and a second parapalindromic sequence of SEQ ID NOS:13,001-25677 or SEQ ID NO:26001-38677 (i.e LeftRegion or RightRegion of Tables 2A-C) and heterologous sequence between the first and second palindromic sequences. Copending claims more broadly claims “a cell” whereas instant claims 4-5 more narrowly recite a eukaryotic cell. However, it would have been obvious to choose from a finite number of predictable cells (i.e. eukaryotic or prokaryotic cells) as the cell of copending claim 22 to predictable arrive at the limitations of instant claims 4-5.
Regarding claims 11-12, copending claim 11 teaches (a) and (b) as discussed above. Copending claim does not teach that the (a) and (b) are in a separate container (claim 11) or admixed (claim 12). However, it would have been obvious to an artisan of ordinary skill that one could store or package in a kit (a) and (b) in separate containers or admixed as that would be the on two obvious for providing storing or packaging in a kit as starting materials.
Regarding claims 14-16, copending claim 11 does not recite that the claimed nuclei acid encoding a recombinase is present in a viral vector (claim 14), more particularly an AAV vector (claim 15). Copending claim 16 also does not teach that the double stranded insert DNA is in a viral vector (claim 16). However, at before the time of filing placing nucleic acids encoding expression cassettes or template nucleic acids for insertion were well established in the prior art for the effective purpose of introducing these elements into a cells. As such, it would have been obvious to include the nucleic acids encoding the recombinase and the template into viral vectors, particularly AAV vectors as claimed.
Regarding claim 17, copending claim 11 disclose that the nucleic acid encoding the recombinase is an mRNA. However, before the time of the copending claim nucleases for the purpose of gene editing where being introduced into cell via mRNA to control expression and presence of the recombinase in the cells. As such, it would have been obvious to introduce the nucleic acid encoding the recombinase in copending claim 11 in the form of an mRNA.
Regarding claim 20, copending claim 11 more broadly recites the genus “a cell” whereas instant claim 20 more narrowly recites “a human cell”. However, it would have been obvious to choose a human cell as the cell used in the copending claim 11 to predictably arrive at the limitations of instant claim 20. One would be motivated to use a human cell as the cell because human cells are relevant to treatment of humans.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632