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 .
Claim 3 has been canceled. Claims 1, 2, 4-17 remain pending.
Applicant's arguments filed 7-7-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicants elected Group I, claims 1-4, 8, 9, 16, 17, without traverse in the reply filed on 12-16-24. Upon reconsideration, claim 5 was combined with Group I.
Claim 1 is drawn to a method of selecting Aukland Island pigs whose genomes do not contain any functional endogenous PERV-C or PERV-A/C. Claim 6 is drawn to a method of breeding pigs that have no function PERV-A, PERV-B, PERV-C, or PERV-A/C genomic sequences. The scope of claims 1 and 6 remain patentably distinct. Likewise, the “pig herd” in claim 7 (dependent on claim 6) remains patentably distinct.
Claims 10-14 could possibly overlap with claims 1-5, 8, 9, 16, 17, but they remain too different and the issues remain too extensive to examine them all together at this time.
The method of treatment in claim 15 as written requires extensive consideration under written description, enablement, indefiniteness and art not required for the product or the method of breeding/making.
Claims 6, 7, 10-15 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 2, 4, 5, 8, 9, 16, 17 remain under consideration.
Claim objection
The phrase “when estimated by PCR-based methods” in claim 1 bears no patentable weight on pigs that have a total copy number of functional and non-functional PERV-A, PERV-B, PERV-C, and PERV-A/C between 40-40. How the copy number is determined makes no different in the structure or function of the pigs.
The phrase “a herd of” in line 1 of step a) is redundant because a plurality of “pigs” (plural) are “provided”.
Step b) of claim 1 requires “selected pigs of the herd of step a), but step does not require selecting ANY pigs. Step a) is limited to “providing” pigs. Step b) can be written more simply as ---sequencing the genomes of the pigs provided in step a)---.
Step c) can be written more simply as ---determining the copy number of functional PERV-C and PERV-A/C in the genomes of the pigs sequenced in step b)---.
Claim 2 should refer to step b) of claim 1, i.e. ---e) determining the number of functional PERV-A and PERV-B in the genomes of the pigs obtained in step b); and f) selecting pigs whose genomes have a total copy number of functional PERV-A and PERV-B between 1 and 10 from the pigs of step e)---.
The phrase “to inactivate” in claim 8 is an intended use and does not bear patentable weight because it does not have to occur. Therefore, the phase fails to set forth any structure or function of the pig. It also fails to invoke process steps. Therefore, the active steps and reagents required to perform the method and the structure/function of the pig obtained at the end are not clearly set forth. Perhaps it would be easier to say ---A method of making a genetically modified Aukland Island pig whose genome does not contain any functional PERV-C or PERV-A/C and has an inactivated alpha-1,3-galactosyltransferase (GGTA1),… …or swine leukocyte antigen (SLA) gene, the method comprising: a)…---.
The optional steps in claim 8 are confusing.
The steps of claim 8 can be written more accurately as ---e) inactivating a GGTA1, CMAH,… or SLA gene in a fibroblast isolated from the pig obtained in claim 1; f) performing somatic cell nuclear transfer from the fibroblast obtained in step a) into an oocyte from a pig whose genome whose genome does not contain any functional PERV-C or PERV-A/C such that a zygote is obtained; and g) transferring the zygote obtained in step b) into the uterus of a pig such that a genetically modified Aukland Island pig whose genome does not contain any functional PERV-C or PERV-A/C and has an inactivated GGTA1,… …or SLA gene is obtained.
.
Claim Interpretation
It is assumed “porcine endogenous retrovirus (PERV)” in step a) of claim 1 encompasses PERV-A, PERV-B, PERV-C, and PERV-A/C discussed in the paragraph bridging pg 1-2, and described by Kimsa (2014). It is assumed the metes and bounds of each were well-known.
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.
Claim Rejections - 35 USC § 112
Written Description
Claims 1, 2, 4, 5, 8, 9, 16, 17 remain 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.
Withdrawn rejections
The rejection regarding the method of claim 1 other than a) providing pigs whose genomes have a total copy number of functional and non-functional PERV-A, PERV-B, PERV-C, and PERV-A/C between 4-40 using the method of Elliott (WO 2006110054);
b) sequencing the genome of the pigs provided in step a);
c) determining the number copies of functional PERV-C and PERV-A/C in the pigs sequenced in step b),
d) selecting pigs whose genomes do not contain any functional copies of PERV-C and PERV-A/C from the pigs sequenced in step c)
has been withdrawn in view of the amendment.
The rejection regarding “identifying the PERV-A and PERV-B status of the PERV-C and PERV-A/C negative pigs of step d) and further selecting pigs whose genomes comprise a total copy number of PERV-A and PERV-B sequences of between 1-10” in claim 2 other than selecting pigs whose genomes contain a total copy number of functional PERV-A and PERV-B sequences between 1-10 has been withdrawn in view of the amendment.
The rejection regarding obtaining any pigs whose genomes do not contain any PERV sequences that are capable of producing PERV particles as required in claim 4 has been withdrawn in view of the amendment.
The rejection regarding a pig whose genome does not contain any functional PERV-C and PERV-A/C as broadly encompassed by claim 5 has been withdrawn in view of the amendment.
A) The specification lacks written description for “(b) establishing a cell line from the pigs of step (a); (c) inactivating a [GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1 or SLA gene] in the cells of the cell line of step b) by gene editing; (d) optionally gene editing selected isolated cells of step (c) to express one or more human genes selected from A20, CD39, CD46, CD47, CD55, CD59, hemoxygenase-1 (HO-1), HLA-E, HLA-G, thrombomodulin (TM), CTLA4-Ig, and LEA29Y; (e) establishing a gene-edited cell line from the pig cells of step (c) or (d); (f) carrying out somatic cell nuclear transfer from one or more of said gene edited cells of step (e) into an oocyte from a whose genome does not contain any functional PERV-C or PERV-A/C in vitro to produce a zygote; (g) optionally culturing zygotes to blastocyst stage; (h) transferring said zygote or blastocyst to a female PERV-C and PERV-A/C negative pig and growing to full term; and (i) providing donor pigs that are PERV-C and PERV-A/C negative and gene edited for one or more xenoantigens” as broadly encompassed by steps b)-h) of claim 8 other than:
e) isolating fibroblasts from the pigs selected in step d);
f) genetically modifying the fibroblasts isolated in step e) such that a GGTA1, CAMH,… gene is inactivated in the fibroblasts;
g) transferring the nucleus of the fibroblast obtained in step f) into an isolated oocyte whose genome lacks any copies of PERV-C and PERV-A/C;
h) culturing the cell obtained in step g) to blastocyst stage;
i) implanting the blastocyst into the uterus of a recipient pig;
j) obtaining a genetically modified pig whose genome lacks any copies of PERV-C and PERV-A/C and comprises an inactivated GGTA1 or CAMH gene from the blastocyst implanted in step i).
Steps b)-e) require establishing a “cell line” from a pig whose genome does not contain any functional PERV-C and PERV-AC.
Steps c)-e) require establishing a “gene-edited cell line” with any inactivated “xenoantigen”. “Xenoantigen” genes includes GGTA1, CAMH, B4GalNT2, Neu5Gc, ASGR1, and SLA (claim 9). However, the metes and bounds of “xenoantigen” genes are unclear (see 112/2nd). The specification gives examples of xenoantigens on pg 3, lines 19-26, e.g. GGTA1 and CMAH, and discusses xenoantigens on pg 19; pg 21, lines 30-35; and pg 22, lines 39-34. However, the specification and the art at the time of filing are limited to inactivating the GGTA1 (Examples 4 and 7), CMAH (Example 5), or both GGTA1 and CMAH (Examples 6 and 8) (pg 21, lines 11-17) (Examples 4-8 on pg 33-43).
Petersen (Xenotransplantation, 2016, Vol. 23, No. 5, pg 338-346) inactivated the GGTA1 gene in pigs.
The specification does not teach the sequence of any pig B4GalNT2, Neu5Gc, ASGR1, or SLA genes, any target sequences within pig B4GalNT2, Neu5Gc, ASGR1, or SLA genes for genetic modification using CRISPR or any other technology that would ensure inactivation of any pig B4GalNT2, Neu5Gc, ASGR1, or SLA gene. An adequate written description of inactivated pig GGTA1, CMAH, B4GalNT2, Neu5Gc, ASGR1, or SLA gene requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of such genes, the sequences of such genes, the target sequences for inactivating such genes, and the means for doing so. It is not sufficient to generically recite a principal biological property, i.e. “inactivate a GGTA1, CMAH, B4GalNT2, Neu5Gc, ASGR1, or SLA gene”, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any such genes, the sequences of such genes, the target sequences required to inactivate such sequences, and the means of doing so. Also, naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, claiming a step of “inactivating a GGTA1, CMAH, B4GalNT2, Neu5Gc, ASGR1, or SLA gene” without defining what means will do is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived.
Steps d)-e) require establishing a cell that optionally express one or more human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y gene. This encompasses humanizing any pig A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y gene (i.e. replacing an endogenous sequence with a human sequence). It also encompasses expressing endogenous and exogenous human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y genes. However, the specification does not teach the sequence of any human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, or LEA29Y genes or expressing them in any pig or pig cell that lacks any copies of a PERV-C and PERV-A/C as required in claim 8. An adequate written description of the pig expressing human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, or LEA29Y genes requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the sequences of such genes and genetically modified pigs that express A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, or LEA29Y genes. It is not sufficient to generically expression of these genes because disclosure of no more than that, as in the instant case, is simply a wish to know the sequences of such genes and pigs that express such genes. Also, naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, claiming a step of expressing human A20, CD39… …or LEA29Y without defining what means will do is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived. It is not readily apparent applicants were reasonably in possession of pigs that lacked any copies of PERV-C and PERV-A/C that expressed human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, or LEA29Y genes as optionally required in claim 8.
Step g) requires “optionally culturing the zygote obtained in step f) to blastocyst stage”; however, the specification is limited to culturing the oocyte obtained in step f) such that a blastocyst is obtained.
Step h) should be limited to implanting “the blastocyst” into the uterus of a pig whose genome lacks any functional PERV-C and PERV-AC sequences and growing “the blastocyst” to full term.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Enablement
Claims 1, 2, 4, 5, 8, 9, 16, 17 remain 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
a) sequencing the genome of pigs;
b) selecting pigs whose genomes contain a total copy number of functional and non-functional PERV sequences between 4-40;
c) selecting pigs whose genomes do not contain any functional PERV-C and PERV-A/C sequences,
does not reasonably provide enablement for the claims as broadly written. 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.
Withdrawn rejections
The rejection regarding the method of claim 1 other than a) providing pigs whose genomes have a total copy number of functional and non-functional PERV-A, PERV-B, PERV-C, and PERV-A/C between 4-40 using the method of Elliott (WO 2006110054);
b) sequencing the genome of the pigs provided in step a);
c) determining the number copies of functional PERV-C and PERV-A/C in the pigs sequenced in step b),
d) selecting pigs whose genomes do not contain any functional copies of PERV-C and PERV-A/C from the pigs sequenced in step c)
has been withdrawn in view of the amendment.
The rejection regarding “identifying the PERV-A and PERV-B status of the PERV-C and PERV-A/C negative pigs of step d) and further selecting pigs whose genomes comprise a total copy number of PERV-A and PERV-B sequences of between 1-10” in claim 2 other than selecting pigs whose genomes contain a total copy number of functional PERV-A and PERV-B sequences between 1-10 has been withdrawn in view of the amendment.
The rejection regarding obtaining any pigs whose genomes do not contain any PERV sequences that are capable of producing PERV particles as required in claim 4 has been withdrawn in view of the amendment.
The rejection regarding a pig whose genome does not contain any functional PERV-C and PERV-A/C as broadly encompassed by claim 5 has been withdrawn in view of the amendment.
A) The specification does not enable making/using a method comprising “(b) establishing a cell line from the pigs of [claim 1]; (c) inactivating a [GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1 or SLA gene] in the cells of the cell line of step b) by gene editing; (d) optionally gene editing selected isolated cells of step (c) to express one or more human genes selected from A20, CD39, CD46, CD47, CD55, CD59, hemoxygenase-1 (HO-1), HLA-E, HLA-G, thrombomodulin (TM), CTLA4-Ig, and LEA29Y; (e) establishing a gene-edited cell line from the pig cells of step (c) or (d); (f) carrying out somatic cell nuclear transfer from one or more of said gene edited cells of step (e) into an oocyte from a whose genome does not contain any functional PERV-C or PERV-A/C in vitro to produce a zygote; (g) optionally culturing zygotes to blastocyst stage; (h) transferring said zygote or blastocyst to a female PERV-C and PERV-A/C negative pig and growing to full term; and (i) providing donor pigs that are PERV-C and PERV-A/C negative and gene edited for one or more xenoantigens” as broadly encompassed by steps b)-h) of claim 8 other than:
e) isolating fibroblasts from the pigs selected in step d);
f) genetically modifying the fibroblasts isolated in step e) such that a GGTA1, CAMH,… gene is inactivated in the fibroblasts;
g) transferring the nucleus of the fibroblast obtained in step f) into an isolated oocyte whose genome lacks any copies of PERV-C and PERV-A/C;
h) culturing the cell obtained in step g) to blastocyst stage;
i) implanting the blastocyst into the uterus of a recipient pig;
j) obtaining a genetically modified pig whose genome lacks any copies of PERV-C and PERV-A/C and comprises an inactivated GGTA1 or CAMH gene from the blastocyst implanted in step i).
Steps b)-e) require establishing a “cell line” from a pig whose genome does not contain any functional PERV-C and PERV-AC.
Steps c)-e) require establishing a “gene-edited cell line” with any inactivated “xenoantigen”. “Xenoantigen” genes includes GGTA1, CAMH, B4GalNT2, Neu5Gc, ASGR1, and SLA (claim 9). However, the metes and bounds of “xenoantigen” genes are unclear (see 112/2nd). The specification gives examples of xenoantigens on pg 3, lines 19-26, e.g. GGTA1 and CMAH, and discusses xenoantigens on pg 19; pg 21, lines 30-35; and pg 22, lines 39-34. However, the specification and the art at the time of filing are limited to inactivating the GGTA1 (Examples 4 and 7), CMAH (Example 5), or both GGTA1 and CMAH (Examples 6 and 8) (pg 21, lines 11-17) (Examples 4-8 on pg 33-43).
Petersen (Xenotransplantation, 2016, Vol. 23, No. 5, pg 338-346) inactivated the GGTA1 gene in pigs.
The specification does not teach the sequence of any pig B4GalNT2, Neu5Gc, ASGR1, or SLA genes, any target sequences within pig B4GalNT2, Neu5Gc, ASGR1, or SLA genes for genetic modification using CRISPR or any other technology that would ensure inactivation of any pig B4GalNT2, Neu5Gc, ASGR1, or SLA gene.
Steps d)-e) require establishing a cell that optionally express one or more human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y gene. This encompasses humanizing any pig A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y gene (i.e. replacing an endogenous sequence with a human sequence). It also encompasses expressing endogenous and exogenous human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, and LEA29Y genes. However, the specification does not teach the sequence of any human A20, CD39, CD46, CD47, CD55, CD59, HO-1, HLA-E, HLA-G, TM, CTLA4-Ig, or LEA29Y genes or expressing them in any pig or pig cell that lacks any copies of a PERV-C and PERV-A/C as required in claim 8.
Step g) requires “optionally culturing the zygote obtained in step f) to blastocyst stage”; however, the specification is limited to culturing the oocyte obtained in step f) such that a blastocyst is obtained.
Step h) should be limited to implanting “the blastocyst” into the uterus of a pig whose genome lacks any functional PERV-C and PERV-AC sequences and growing “the blastocyst” to full term.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Indefiniteness
It is assumed the metes and bounds of “porcine endogenous retrovirus (PERV)” in step a) of claim 1 encompasses PERV-A, PERV-B, PERV-C, and PERV-A/C discussed in the paragraph bridging pg 1-2, and described by Kimsa (2014) and that the metes and bounds of each were well-known.
Claims 1, 2, 4, 5, 8, 9, 16, 17 remain 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.
Withdrawn rejections
The rejection of claim 1 has been withdrawn in view of the amendment.
The rejection of claim 8 has been withdrawn in view of the amendment.
New/Pending rejections
A) The phrase “selected pigs” in claim 1 step b) lacks antecedent basis. Step a) does not require selecting anything.
B) Claims 16 and 17 remain indefinite because it is unclear whether “the selecting” is the “further selecting pigs” with very low PERV-A and -B in claim 2 or the “selecting PERV-C and PERV-AC negative” pigs in claim 1.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
Claims 1, 2, 4, 5, 16, 17 remain rejected under 35 U.S.C. 102a1 as being anticipated by Elliott (WO 2006110054).
Elliott taught how to sequence, test, select, and breed Auckland Island pigs that lack the microorganisms listed in step a) of claim 1 and selecting pigs whose genomes contain 0-30 copies of functional or non-functional PERV sequences. This is acknowledged by applicants on pg 2, line 13. The Summary of the Invention of Elliott broadly describes testing, selecting, and breeding pigs with low PERV copies, and pg 10, lines 21-29 described well-known classes of PERV-A, PERV-B, PERV-C, and PERV-A/C. Elliott specifically selected pigs lacking PERV-C (throughout; claim 2, 18, 19, 21, 22, 28). Pg 36, line 20, of Elliott discusses PERV-AC and cites reference 10, i.e. Gemeniano (2006, Virology, Vol. 346, No. 1, pg 108-117). Example 2 of Elliott specifically tested/selected for three classes of PERV (PERV-A, PERV-B, PERV-C) in Auckland Island pigs, but is not limited to testing just three because of the broad disclosure in the Summary of the Invention and because Elliott specifically disclosed the well-known sequence for PERV-A/C.
Elliott taught: “Methods to determine or observe PERV copy number include various genomic screening methods and other methods known in the art to be suitable to determine or observe the number of copies of a particular nucleic acid sequence in the genome of an organism. Examples of such methods are presented herein in the examples. The present invention further provides organs, tissues or cells isolated from one or more pigs produced by the method of the invention, said organs, tissues or cells being free of infectious microorganisms and having a PERV copy number of between 0 and 30, and are particularly suitable for transplantation into a xenogeneic subject, including a human subject.” The examples go on to test PERV copy number which can ONLY be done by isolating genomic DNA (because PERV integrates into the genome of pigs) “Two techniques were used to calculate PERV proviral number in the pig genome: LightCycler (Roche), and PCR limiting dilution assay (PLDA) with computational analysis using QUALITY (Rodrigo et al, ubik.microbiol.washington.edu/computing)” (Example 2). This is equivalent to “sequencing the genome of the pigs” as required in step c) of claim 1.
Therefore Elliott taught providing a pig herd with a PERV copy number of 4-40 as required in step a) of claim 1, selecting pigs to be sequenced in step b), sequencing the genomes in step c) and selecting pigs whose genomes do not contain any functional PERV-C or PERV-A/C sequences as required in steps d) and e).
Elliott taught identifying genomic sequences of each pig that were PERV negative, specifically taught doing so using well known sequences for PERV-C and PERV-AC, and exemplified doing so using PERV-C as an example. Elliott taught selecting genomic sequences of each pig that were PERV negative, specifically taught doing so using well known sequences for PERV-C and PERV-AC, and do so using PERV-A, -B, and -C as examples (Example 2). Elliott referenced the well-known sequence of PERV-AC of Gemeniano. This is all that is required to meet the limitation of “selecting pigs whose genomes do not contain any functional PERV-C and PERV-AC sequences” as required in step e) of claim 1. Elliott need not exemplify testing for PERV-AC to meet the limitation because it was taught and inferred. Especially because Elliott taught selecting pigs that lacked any PERV sequences in their genome (claim 1) which must mean the pigs lacked any PERV-C, or -AC as required in step e) of claim 1.
Claim 2 has been included because Elliott taught identifying PERV-A and -B status and selecting pigs whose genome had 1-10 copies of PERV-A and -B in Example 2.
Elliott taught the pigs lacked any PERV in their genome (claim 1) as required in claim 4.
Elliott taught selecting 0-30 copies of PERV (claim 1) which encompasses 1-5 or 1-2 copies as required in claims 16 and 17.
Response to arguments
Applicants argue Elliott is limited to using PCR to test for PERV sequences as compared to “genome sequencing” (pg 17). Applicants’ argument is not persuasive. Perhaps applicants are attempting to argue Elliott did not sequence the entire genome of the pigs. However, claim 1 makes no requirement of sequencing the entire genome of each pig. Furthermore, the PCR method described by Elliott MUST start with isolating genomic DNA and making a determination of whether PERV sequences are present within the genomic DNA of each pig. This is equivalent to “sequencing the genome of selected pigs” as required in step b) of claim 1. Pg 24, line 24, exemplifies using PCR to determine PERV genome sequences, so the method of Elliott is clearly part of the invention.
Applicants point to para 11-12 of the Declaration filed 7-7-26 which says genome sequencing is the only way to determine the copy number of full length PERVs. The Declaration is not persuasive because Elliott and applicants’ examples use PCR to determine the presence of functional PERVs in the genome of pigs.
Claim Rejections - 35 USC § 103
A) Claims 1, 2, 4, 5, 16, 17 remain rejected under 35 U.S.C. 103 as being unpatentable over Elliott (WO 2006110054) in view of Gemeniano (2006, Virology, Vol. 346, No. 1, pg 108-117) and Wood (J. Virol., 2004, Vol. 78, No. 5, pg 2494-2501).
This rejections addresses the fact that Elliott did not exemplify testing for PERV-AC status. This is not in conflict with the anticipation rejection. It is simply provided in case it is found that a higher standard is required to meet the embodiment of testing for PERV-AC status encompassed by claim 1.
Elliott taught how to sequence, select, and breed Auckland Island pigs based on PERV status for reasons set forth above. Specifically, Elliott taught, suggested, and inferred testing PERV-AC status and identifying, selecting, and breeding PERV-AC negative pigs for reasons cited above. In particular, the PERV copy number of 0-30 in claim 1 of Elliott encompasses pigs with 0-30 PERV-AC.
Elliott did not exemplify testing for PERV-AC status and identifying pigs that were PERV-AC negative as encompassed by claim 1.
However, testing for PERV-AC status and identifying PERV-AC negative status in pigs was described by Gemeniano (pg 110, Fig. 2; pg 113, Fig. 7). Wood tested and identified PERV-A, -B, -C, and -AC in the genome of pigs (abstract; Materials and Methods) for the purpose of improving pig tissue for xenotransplantation (abstract, Summary).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to test/identify/select pigs that were PERV-A, -B, and -C negative as described by Elliott and testing for PERV-AC status and identify PERV-AC negative status as described by Gemeniano and Wood. Those of ordinary skill in the art at the time of filing would have been motivated to test/identify/select pigs that were PERV-AC negative because Elliott taught identifying/selecting pigs that had a PERV copy of 0 (claim 1) which includes zero copies of PERV-AC. Those of ordinary skill in the art at the time of filing would have been motivated to test/identify/select pigs with 0 copies of PERV-AC for improved xenotransplantation. Those of skill would have had a reasonable expectation of successfully testing for PERV-AC status in pigs because Gemeniano and Wood taught how to test PERV-AC status in pig cells and because Elliott tested PERV-A, -B, and -C status in Example 2.
Claim 2 has been included because Elliott taught identifying PERV-A and -B status and selecting pigs whose genome had 1-10 copies of PERV-A and -B in Example 2.
Elliott taught the pigs lacked any PERV in their genome (claim 1) as required in claim 4.
Elliott taught selecting 0-30 copies of PERV (claim 1) which encompasses 1-5 or 1-2 copies as required in claims 16 and 17.
Response to arguments
Applicants point to para 13, 17 of the Declaration which says Elliott did not generate genomic sequencing data and did not determine whether PERV sequences were functional or non-functional. The declaration is not persuasive. Elliott MUST have tested genomic DNA and determined whether PERV sequences were present which is equivalent to “sequencing the genome of selected pigs” as required in step b) of claim 1. Pg 24, line 24, exemplifies using PCR to determine PERV genome sequences, so the method of Elliott is clearly part of the invention. Step a) just requires “providing” pigs with a total of 4-40 “functional and non-functional” PERV sequences which is not the same thing as sequencing the entire genome of a pig and selecting pigs whose genomes have 4-40 “functional and non-functional” PERV sequences as discussed in para 17 of the declaration.
Applicants’ discussion of Yang on pg 19-20 has nothing to do with the rejection at hand.
Applicants point to para 25-28 of the declaration which discuss PCR-based determination of PERVs. The Declaration is not persuasive because the claims are not limited to sequence the entire genome of a pig.
Applicants somehow come to a conclusion on pg 22 that para 25-28 are evidence of unexpected results. Applicants’ conclusion is not tenable because it is unfounded. Para 25-28 are limited to sequencing the entire genome of each pig, but the claims are not. Applicants’ argument and para 25-28 cannot be an “unexpected results” argument because it does not start with what was expected, take secondary considerations into account, or compare what was expected to applicants’ results.
B) Claims 1, 2, 4, 5, 8, 9, 16, 17 remain rejected under 35 U.S.C. 103 as being unpatentable over Elliott (WO 2006110054) in view of Kurome (Methods Mol. Biol., 2015, Vol. 1222, pg 37-59) and Petersen (Xenotransplantation, 2016, Vol. 23, No. 5, pg 338-346).
Elliott taught how to sequence, select, and breed Auckland Island pigs with 0-30 copies of PERV sequences in their genome. This is acknowledged by applicants on pg 2, line 13. The starting herd of Elliott is a pig herd with a PERV copy number of 4-40 as required in step a) of claim 1. The Summary of the Invention of Elliott broadly describes testing, selecting, and breeding pigs with low PERV copies, and pg 10, lines 21-29 described well-known classes of PERV-A, PERV-B, PERV-C, and PERV-A/C. Elliott specifically selected pigs lacking PERV-C (throughout; claim 2, 18, 19, 21, 22, 28). Pg 36, line 20, of Elliott discusses PERV-AC and cites reference 10, i.e. Gemeniano (2006, Virology, Vol. 346, No. 1, pg 108-117). Example 2 of Elliott specifically tested/selected for three classes of PERV (PERV-A, PERV-B, PERV-C), but is not limited to testing just three because of the broad disclosure in the Summary of the Invention and because Elliott specifically disclosed the well-known sequence for PERV-A/C.
Elliott sequenced the genome of each pig to determine the PERV status (cited above) which is equivalent to step b) of claim 1.
Elliott taught identifying genomic sequences of each pig that were PERV negative, specifically taught doing so using well known sequences for PERV-C and PERV-AC, and exemplified doing so using PERV-C as an example. This is all that is required to meet the limitation of “identifying individual pigs that have PERV-C and PERV-AC negative status” as required in claim c). Elliott need not exemplify testing for PERV-AC to meet the limitation because it was taught and inferred.
Elliott taught selecting pigs that lacked any PERV in their genome (claim 1) which must mean the pigs lacked any PERV-C, or -AC as required in step d) of claim 1. Elliott taught selecting genomic sequences of each pig that were PERV negative, specifically taught doing so using well known sequences for PERV-C and PERV-AC, and do so using PERV-A, -B, and -C as examples (Example 2). The lack of any PERV sequences in claim 1 of Elliott and the disclosure of Elliott as a whole are all equivalent to “selecting said PERV-C and PERV-AC negative pigs” as required in claim c). Elliott need not exemplify selecting PERV-AC negative pigs to meet the limitation because it is inferred in claim 1 of Elliott, because it was taught and inferred throughout the disclosure of Elliott, and because Elliott referenced the well-known sequence of PERV-AC of Gemeniano.
Elliott did not teach inactivating a GGTA1 gene in the pig as encompassed by step c) of claim 8. However, inactivating a GGTA1 gene in a pig cell was described by Petersen (Materials and Methods). Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to test/identify/select pigs that were PERV-C and -AC negative as described by Elliott and inactivate the GGTA1 gene as described by Petersen. Those of ordinary skill in the art at the time of filing would have been motivated to inactivate the GGTA1 gene in pigs that were PERV-C and -AC via SCNT to decrease the likelihood of rejection of pig tissue after xenotransplantation (Petersen abstract and throughout). Those of skill would have had a reasonable expectation of successfully inactivating the GGTA1 gene in the pigs of Elliott via the means described by Petersen because Petersen successfully did so (Results).
Elliott did not teach somatic cell nuclear transfer (SCNT) as required in steps f)-i) of claim 8. However, SCNT in pig cells was described by Kurome (Materials and Methods). Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to test/identify/select pigs that were PERV-C and -AC negative as described by Elliott and clone them via SCNT as described by Kurome. Those of ordinary skill in the art at the time of filing would have been motivated to clone pigs that were PERV-C and -AC via SCNT to “facilitate the generation of tailored pig models for biomedical research and for xenotransplantation” (Kurome abstract). Those of skill would have had a reasonable expectation of successfully cloning the pigs of Elliott via SCNT described by Kurome because Kurome taught a number of SCNT strategies and a number of examples of SCNT in pigs in references 1-7 cited on pg 38-39 (see pg 59).
Claim 2, 4, 5, 16, 17 have been included for reasons set forth above.
Claim 9 has been included because it specifies inactivating a GGTA1 gene.
Response to arguments
Applicants do not specifically address this rejection.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
