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 .
Claims 1-43 have been canceled. Claims 44-73 have been added.
Specification
The title will have to be changed to more closely reflect the claimed subject matter.
Claim Interpretations/Objections
It is assumed “porcine endogenous retrovirus (PERV)” in claim 44 encompasses PERV-A, PERV-B, PERV-C, and PERV-A/C described by Kimsa (Viruses, 2014, Vol. 6, pg 2062-2083).
It was well-known how to test, select, and breed pigs with 0-30 copies of PERV as required in step a) of claim 1 using the method described by Elliott (WO 2006110054) (pg 2, line 13, of the specification). Elliott taught testing, selecting, and breeding pigs with low PERV copies generically throughout the disclosure (Summary of the Invention), described well-known classes of PERV-A, PERV-B, PERV-C, and PERV-A/C (pg 10, lines 21-29), tested specifically for three classes of PERV (Example 2, PERV-A, PERV-B, PERV-C), and taught specifically selecting pigs lacking PERV-C (throughout; claim 2, 18, 19, 21, 22, 28). PERV-A/C is cited by Elliott on pg 10, lines 27-29, in reference 10, Gemeniano (2006, Virology, Vol. 346, No. 1, pg 108-117) (pg 36, line 20).
Pg 109, col. 1, lines 10-13, of Gemeniano says PERV-AC is also known as PERV-14/220.
It is assumed that the genome of all wild-type porcine (pig) cells have a plurality of “porcine endogenous retrovirus” (PERV) sequences.
It is assumed all PERV sequence in a wild-type pig cell have a pol gene.
The second occurrence of PERV in claim 44 does not have to be spelled out before being abbreviated.
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.
Enablement
Claims 44-73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for genetically modified pig cells whose genomes comprise inactivated porcine endogenous retroviral (PERV) sequences, does not reasonably provide enablement for genetically modified pig cells in which 20% of PERV pol genes within the genome of the cells comprise any genetically engineered genomic mutation. 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/use the invention commensurate in scope with these claims.
A) The specification does not enable making or using any genetically modified pig cells in which 20% of PERV pol genes within the genome of the cells comprise any genetically engineered genomic mutation as broadly encompassed by claim 44.
Claim 44 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation.
Claim 44 encompasses pig cells comprising complete PERV sequences comprising a PERV pol gene or just PERV pol genes. The pol gene may be genomic or episomal. The genetic modification of the PERV pol gene may encode a wild-type pol protein or have any mutation that maintains the function of pol. It also encompasses any genetic modification that increases pol activity as well as any genetic modification that decreases pol activity by any amount. It also encompasses inactivating a pol gene.
See also claim interpretation above.
The specification and the art at the time of filing are limited to a pig cell that inherently contains a plurality of PERV sequences in its genome and genetically modifying the pol gene of at least 20% of the PERV sequences so that the pol gene is inactivated (Examples).
The specification and the art do not correlate pig cells comprising a plurality of complete PERV sequences (including a PERV pol gene) to cells comprising just PERV pol genes as broadly encompassed by claim 44. The specification does not correlate pig cells whose genome comprises a plurality of complete PERV sequences (each comprising a pol gene) to episomal PERV sequences as broadly encompassed by claim 44. The specification does not correlate inactivating the pol gene in at least 20% of genome PERV sequences to any genetic modification of the PERV pol gene that encodes a wild-type pol protein, has any mutation that maintains the function of pol, any genetic modification that increases pol activity, or any genetic modification that merely decreases pol activity by a little bit.
Claims 59-61 further limit the mutation [of the PERV pol gene] to any “indel” or deletion of less than 149 base pairs or a deletion of less than 9 base pairs. Claims 59-61 are included for reasons cited above because they encompass any indel or deletion encoding any wild-type pol, or any indel or deletion that decreases pol activity without inactivating pol activity.
Claims 62-64 say at least 80%, 90%, or 97% of the PERV pol genes have a genetic modification but do not say the PERV pol genes are part of complete PERV sequences in the genome of the pig cells. They are also included for reasons cited above because they encompass any indel or deletion encoding any wild-type pol, or any indel or deletion that decreases pol activity without inactivating pol activity.
B) The specification does not enable a plurality of PERV pol genes that have “5 [or 60] or more retrovirus genes” as required in claims 45 and 46. An entire PERV sequence may include numerous genes, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46. At least 5 PERV pol genes may be inactivated in the genome of the pig cell, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46
C) The specification does not enable making or using any genetically modified pig cells in which PERV gag or env genes are intact as broadly encompassed by claim 47. Claim 47 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, and further contains intact PERV gag and/or env genes. Claim 47 encompasses pig cells comprising complete PERV sequences comprising PERV gag or env genes or just PERV gag or env genes. The gag or env genes may be genomic or episomal. The specification and the art at the time of filing are limited to a pig cell that inherently contains a plurality of PERV sequences in its genome and genetically modifying the pol gene of at least 20% of the PERV sequences so that the pol gene is inactivated (Examples). The PERV gag or env genes (in the genomic PERV sequences) remain intact. The specification and the art do not correlate pig cells comprising a plurality of complete PERV sequences (including PERV gag or env genes) to cells comprising just PERV pol and PERV gag or env genes as broadly encompassed by claim 47. The specification does not correlate pig cells whose genome comprises a plurality of complete PERV sequences (each comprising pol, gag or env genes) to episomal PERV gag or env genes as broadly encompassed by claim 47.
D) The specification does not enable making or using any genetically modified pig cells that exhibit at least 1000X reduced PERV transmission as evidenced by co-culture with any second cell as compared to co-culturing the second cell with a wild-type pig cell. as broadly encompassed by claim 51.
Claim 51 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, wherein the genetically engineered porcine cell exhibits at least a 1000-fold reduction in PERV transmission, as evidenced by co-culturing a second cell with the genetically engineered porcine cell, as compared to co-culturing the second cell with a wild-type porcine cell.
The claim does not make sense without the second cell being a pig cell, a step of fertilization, an offspring, or at least another mammalian cell that is susceptible to infection by PERV in culture. Claim 51 encompasses using cells that have PERV sequences already or cells that have none. Claims 52 says the second cell is a human cell, but the specification and the art at the time of filing do not correlate human or any other mammalian cell to any “second cell” as broadly encompassed by claim 51. The specification does not correlate using a second cell that is a human cell [that presumably does not contain PERV sequences] to using any second cell that is a pig cell whose genome comprises PERV sequences.
To complicate matters, claim 51 reads as a method of using the product without any clear active steps. The method steps do not alter the structure/function of the cells themselves. If applicants are attempting to capture a capability of the cell when co-cultured (with another cell that does not contain PERV sequences), then that capability must be more clearly set forth.
Claims 52 and 53 further limit the second cell which does nothing to further limit the structure/function of the cells in claim 51.
Claims 54-56 further limit the amount of time the pig cells and second cells are in co-culture which does nothing to further limit the structure/function of the cells in claim 51.
Claims 57 and 58 further limit how PERV transmission is assessed in the co-culture which does nothing to further limit the structure/function of the cells in claim 51.
E) The specification does not enable making or using any genetically modified pig cells in which the genetic modification is observed by sequencing as required in claim 66.
Claim 66 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, wherein the genetic mutation is observed by sequencing.
Claim 66 reads as a method of using the product without any clear active steps. The method step of performing sequencing does not alter the structure/function of the cells themselves. If applicants are attempting to capture a capability of the cell, then that capability is wholly unclear.
F) The specification does not enable any progeny cell, tissue, organ, or pig as required in claims 67-71 other than cells, tissues, organs, or pigs whose genomes comprise at least 20% of their genomic PERV sequences inactivated for reasons cited above.
G) The specification does not enable any pig cells as broadly encompassed by claims 72 and 73 other than cells, tissues, organs, or pigs whose genomes comprise at least 20% of their genomic PERV sequences inactivated for reasons cited above.
Written Description
Claims 44-73 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.
A) The specification lacks written description for any genetically modified pig cells in which 20% of PERV pol genes within the genome of the cells comprise any genetically engineered genomic mutation as broadly encompassed by claim 44.
Claim 44 and its breadth are discussed above. See also claim interpretation above.
The specification and the art at the time of filing are limited to a pig cell that inherently contains a plurality of PERV sequences in its genome and genetically modifying the pol gene of at least 20% of the PERV sequences so that the pol gene is inactivated (Examples).
The specification and the art do not correlate pig cells comprising a plurality of complete PERV sequences (including a PERV pol gene) to cells comprising just PERV pol genes as broadly encompassed by claim 44. The specification does not correlate pig cells whose genome comprises a plurality of complete PERV sequences (each comprising a pol gene) to episomal PERV sequences as broadly encompassed by claim 44. The specification does not correlate inactivating the pol gene in at least 20% of genome PERV sequences to any genetic modification of the PERV pol gene that encodes a wild-type pol protein, has any mutation that maintains the function of pol, any genetic modification that increases pol activity, or any genetic modification that merely decreases pol activity by a little bit.
Claims 59-61 further limit the mutation [of the PERV pol gene] to any “indel” or deletion of less than 149 base pairs or a deletion of less than 9 base pairs. Claims 59-61 are included for reasons cited above because they encompass any indel or deletion encoding any wild-type pol, or any indel or deletion that decreases pol activity without inactivating pol activity.
Claims 62-64 say at least 80%, 90%, or 97% of the PERV pol genes have a genetic modification but do not say the PERV pol genes are part of complete PERV sequences in the genome of the pig cells. They are also included for reasons cited above because they encompass any indel or deletion encoding any wild-type pol, or any indel or deletion that decreases pol activity without inactivating pol activity.
B) The specification lacks written description for a plurality of PERV pol genes that have “5 [or 60] or more retrovirus genes” as required in claims 45 and 46. An entire PERV sequence may include numerous genes, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46. At least 5 PERV pol genes may be inactivated in the genome of the pig cell, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46.
C) The specification lacks written description for any genetically modified pig cells in which PERV gag or env genes are intact as broadly encompassed by claim 47. Claim 47 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, and further contains intact PERV gag and/or env genes. Claim 47 encompasses pig cells comprising complete PERV sequences comprising PERV gag or env genes or just PERV gag or env genes. The gag or env genes may be genomic or episomal. The specification and the art at the time of filing are limited to a pig cell that inherently contains a plurality of PERV sequences in its genome and genetically modifying the pol gene of at least 20% of the PERV sequences so that the pol gene is inactivated (Examples). The PERV gag or env genes (in the genomic PERV sequences) remain intact. The specification and the art do not correlate pig cells comprising a plurality of complete PERV sequences (including PERV gag or env genes) to cells comprising just PERV pol and PERV gag or env genes as broadly encompassed by claim 47. The specification does not correlate pig cells whose genome comprises a plurality of complete PERV sequences (each comprising pol, gag or env genes) to episomal PERV gag or env genes as broadly encompassed by claim 47.
D) The specification lacks written description for any genetically modified pig cells that exhibit at least 1000X reduced PERV transmission as evidenced by co-culture with any second cell as compared to co-culturing the second cell with a wild-type pig cell. as broadly encompassed by claim 51.
Claim 51 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, wherein the genetically engineered porcine cell exhibits at least a 1000-fold reduction in PERV transmission, as evidenced by co-culturing a second cell with the genetically engineered porcine cell, as compared to co-culturing the second cell with a wild-type porcine cell.
The claim does not make sense without the second cell being a pig cell, a step of fertilization, an offspring, or at least another mammalian cell that is susceptible to infection by PERV in culture. Claim 51 encompasses using cells that have PERV sequences already or cells that have none. Claims 52 says the second cell is a human cell, but the specification and the art at the time of filing do not correlate human or any other mammalian cell to any “second cell” as broadly encompassed by claim 51. The specification does not correlate using a second cell that is a human cell [that presumably does not contain PERV sequences] to using any second cell that is a pig cell whose genome comprises PERV sequences.
To complicate matters, claim 51 reads as a method of using the product without any clear active steps. The method steps do not alter the structure/function of the cells themselves. If applicants are attempting to capture a capability of the cell when co-cultured (with another cell that does not contain PERV sequences), then that capability must be more clearly set forth.
Claims 52 and 53 further limit the second cell which does nothing to further limit the structure/function of the cells in claim 51.
Claims 54-56 further limit the amount of time the pig cells and second cells are in co-culture which does nothing to further limit the structure/function of the cells in claim 51.
Claims 57 and 58 further limit how PERV transmission is assessed in the co-culture which does nothing to further limit the structure/function of the cells in claim 51.
E) The specification lacks written description for any genetically modified pig cells in which the genetic modification is observed by sequencing as required in claim 66.
Claim 66 is drawn to a genetically engineered porcine cell containing a plurality of porcine endogenous retrovirus (PERV) pol genes and in which at least 20% of the porcine endogenous retrovirus PERV pol genes comprise a genetically engineered genomic mutation, wherein the genetic mutation is observed by sequencing.
Claim 66 reads as a method of using the product without any clear active steps. The method step of performing sequencing does not alter the structure/function of the cells themselves. If applicants are attempting to capture a capability of the cell, then that capability is wholly unclear.
F) The specification lacks written description for any progeny cell, tissue, organ, or pig as required in claims 67-71 other than cells, tissues, organs, or pigs whose genomes comprise at least 20% of their genomic PERV sequences inactivated for reasons cited above.
G) The specification lacks written description for any pig cells as broadly encompassed by claims 72 and 73 other than cells, tissues, organs, or pigs whose genomes comprise at least 20% of their genomic PERV sequences inactivated for reasons cited above.
Indefiniteness
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 45, 46, 51-58, 66, 72, 73 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.
A) Claims 45 and 46 are indefinite because a singular PERV pol gene does not “include 5 [or 60] or more retrovirus genes”. An entire PERV sequence may include numerous genes, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46. At least 5 PERV pol genes may be inactivated in the genome of the pig cell, but a PERV pol gene does not have 5 [or 60] or more retrovirus genes as required in claims 45 and 46.
B) Claims 51-58 are indefinite. Claim 51 is recited above and reads as a method of using the product without any clear active steps. The method steps do not alter the structure/function of the cells themselves. If applicants are attempting to capture a capability of the cell when co-cultured (with another cell that does not contain PERV sequences), then that capability must be more clearly set forth.
Claims 52 and 53 further limit the second cell which does nothing to further limit the structure/function of the cells in claim 51.
Claims 54-56 further limit the amount of time the pig cells and second cells are in co-culture which does nothing to further limit the structure/function of the cells in claim 51.
Claims 57 and 58 further limit how PERV transmission is assessed in the co-culture which does nothing to further limit the structure/function of the cells in claim 51.
Claims 72 and 73 are indefinite for reasons set forth above because they include “as evidenced by co-culturing”.
C) Claim 66 is indefinite because it further limits how the genomic mutation is observed which does nothing to further limit the structure/function of the cells in claim 41.
The art at the time of filing did not reasonably teach or suggest a genetically modified pig cell in which at least 20% of genomic porcine endogenous retrovirus (PERV) pol genes have been genetically modified.
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.
Claims 44-73 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10952843, 10188510, 9907649 and 9308084. Although the claims at issue are not identical, they are not patentably distinct from each other because they all require a genetically modified pig cell in which at least 20% of genomic porcine endogenous retrovirus (PERV) pol genes have been genetically modified. The pig organs in ‘843 and ‘510, and the method of making pig cells in ‘084 are obvious variants of the pig cells claimed. The pig cells in ‘649 overlap in scope with the pig cells in this application.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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