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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12-18-25 has been entered.
Claim 3 has been canceled. Claims 1, 2, 4-17 remain pending.
Applicant's arguments filed 12-18-25 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 making a herd of Aukland Island 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. 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 are 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Claims 6, 7, 10-15 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 first occurrence of PERV in claim 1 should have the abbreviation spelled out; not the last.
It is unclear whether the claim set should refer to PERV sequences in the genomes of pigs or simply refer to PERV in the genomes of pigs. Currently, the claim set uses both, but please pick one or the other. See the end of step a) and d) in claim 1, for example, which use different phraseology.
The preamble and the final step of claim 1 should have a nexus, i.e. ---A method of selecting pigs whose genomes do not contain any functional PERV-C or PERV-A/C… …selecting pigs whose genomes do not contain any functional PERV-C or PERV-A/C from the pigs obtained in step d)---.
The phrase “selecting” in step b) of claim 1 is meaningless because the pigs whose genomes are sequenced in step c) are inherently “selected”. Delete the “selecting” step.
Claim 2 should refer to step c) of claim 1, i.e. ---f) determining the number of functional PERV-A and PERV-B in the genomes of the pigs obtained in step e); and g) selecting pigs whose genomes have a total copy number of functional PERV-A and PERV-B between 1 and 10---.
Claim 4 should use language in claim 1, i.e. ---wherein the genomes of the pigs selected in step e) do not contain any functional PERV sequences---.
Claim 5 should refer to PERV sequences for consistency, i.e. ---A pig whose genome does not contain any functional PERV sequences obtained from the method of claim 1---.
The preamble Claim 8 should either set forth the structure/use of the pig obtained more clearly (having an inactivated GGTA1, CMAH, B4GalNT2, Neu5Gc, ASGR1 or SLA gene while overexpressing A20, CD39, CD46…, or LEA29Y) or just keep going with the method steps, i.e. The method of claim 1 further comprising: f) establishing a cell line from the pigs obtained in step e), g) inactivating a GGTA1,… …or SLA gene in the cell line….
The “gene editing” by “eliminat[ing] or deactivat[ing]” in step c) of claim 8 can be written more clearly as ---inactivating an alpha-1,3-galactosyltransferase (GGTA1) gene,… …or a swine leukocyte antigen (SLA) gene in the cell line obtained in step b)---.
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.
A) The specification lacks written description for 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 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).
Claim 1 is recited above.
Elliott (WO 2006110054) (cited on pg 2, line 13, of the specification) 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).
Wood (J. Virol., 2004, Vol. 78, No. 5, pg 2494-2501) 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).
PERV-A/C in claim 1 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) also known as PERV-14/220 (see Gemeniano, pg 109, col. 1, line 10-13). PERV-A/C is also discussed in Harrison (J. Virol., 2004, Vol. 78, No. 24, pg 13871-13879) (cited by Gemeniano) and in Kimsa (Viruses, 2014, Vol. 6, pg 2062-2083) (cited by applicants on pg 2, line 1).
The preamble of claim 1 requires “selecting PERV-C and PERV-A/C negative” pigs. Step a) makes the distinction of pigs with total copy number of functional and non-functional PERV between 4-40. The final step of claim 1 requires selecting pigs whose genomes do not contain any functional PERV-C or -AC which encompasses selecting pigs whose genomes contain non-functional PERV-C or -AC but do not contain any functional PERV-C or -AC. This does not make sense because a pig that is “PERV-C and PERV-A/C negative” must have genomes that do not contain any functional or non-functional PERV-C or -AC. There should be a nexus with the preamble and the final pigs selected. Perhaps claim 1 should be limited to selecting pigs whose genomes do not contain any functional or non-functional PERV-C or -AC. Or perhaps applicants are attempting to say the genome of the pigs lack functional PERV-C or -AC, but may contain non-functional PERV-C or -AC. In that case, the pigs are not PERV-C or -AC “negative” as inferred by the preamble. Clarification is required.
Step c) of claim 1 requires sequencing the genome of the pigs obtained in step b), but this must have already occurred to provide pigs whose genomes have a total copy number of function and non-functional PERV between 4-40 using the method of Elliott. Clarification is required.
Perhaps claim 1 should be limited to:
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.
Accordingly, the specification lacks written description for claim 1 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. In particular, it is impossible to provide PERV-C and PERV-A/C negative pigs (preamble; step c) from pigs that have no “functional PERV-C and PERV-A/C” but may contain non-functional PERV-C or -AC as encompassed by the final step.
B) The specification lacks written description for “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. The specification and the art at the time of filing are limited to selecting pigs whose genomes contain a total copy number of functional PERV-A and PERV-B sequences between 1-10 for reasons set forth above. The specification does not correlate these limited steps to the broader embodiments of claim 2. Accordingly, the specification lacks written description for claim 2 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
C) The specification lacks written description for any pigs whose genomes do not contain any PERV sequences that are capable of producing PERV particles as required in claim 4. The specification and the art at the time of filing are limited to selecting pigs whose genomes do not contain any functional PERV sequences for reasons set forth above. The specification does not correlate these limited steps to the broader embodiments of claim 4. Accordingly, the specification lacks written description for claim 4 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. In particular, it is impossible to provide PERV null pigs (claim 4) from pigs that have 4-40 copies of PERV-C and PERV-A/C (step a).
D) The specification lacks written description for a pig whose genome does not contain any functional PERV-C and PERV-A/C as broadly encompassed by claim 5 for reasons set forth above.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
E) The specification lacks written description for the method of claim 8 for reasons set forth in rejection A) if step a) of claim 8 is attempting to further limit the method of claim 1.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
F) The specification lacks written description for “(b) establishing a PERV-C and PERV-A/C negative cell line from the pigs of step (a); (c) gene editing cells of said cells of step (b) to eliminate or deactivate GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1 or SLA; (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 PERV-C and PERV-A/C negative pig 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 “gene-edited cell line”; however, the specification is limited to making a pig cell whose genome lacks any copies of PERV-C and PERV-AC for reasons set forth above.
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 “xenoantigen” 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 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. “eliminate or deactivate one or more xenoantigen genes”, 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 “eliminat[ing] or deactivat[ing] one or more xenoantigen genes” 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 “gene-edited cell line” 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 “eliminat[ing] or deactivat[ing] one or more xenoantigen genes” 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.
The oocyte in step f) may be “from a PERV-C and PERV-AC negative pig”, but the specification is limited to an oocyte whose genome lacks any copies of PERV-C and PERV-AC which is missing from the step. The pig may be a founder that does not have oocytes that lack any copies of PERV-C and PERV-AC; the oocyte in step f) MUST have a genome that lacks any copies of PERV-C and PERV-AC.
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.
A) The specification does not enable using the method of claim 1 other than
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 using the method of Elliott (WO 2006110054);
c) selecting pigs whose genomes do not contain any functional PERV-C and PERV-A/C sequences.
Claim 1 is recited above.
Elliott (WO 2006110054) (cited on pg 2, line 13, of the specification) taught sequencing, 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), sequenced the genome of pigs and tested specifically for three classes of PERV (Example 2, PERV-A, PERV-B, PERV-C), and taught specifically selecting pigs whose genomes lacked PERV-C (throughout; claim 2, 18, 19, 21, 22, 28).
Wood (J. Virol., 2004, Vol. 78, No. 5, pg 2494-2501) 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).
PERV-A/C in claim 1 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) also known as PERV-14/220 (see Gemeniano, pg 109, col. 1, line 10-13). PERV-A/C is also discussed in Harrison (J. Virol., 2004, Vol. 78, No. 24, pg 13871-13879) (cited by Gemeniano) and in Kimsa (Viruses, 2014, Vol. 6, pg 2062-2083) (cited by applicants on pg 2, line 1).
The preamble of claim 1 requires “selecting PERV-C and PERV-A/C negative” pigs. Step a) makes the distinction of pigs with total copy number of functional and non-functional PERV between 4-40. The final step of claim 1 requires selecting pigs whose genomes do not contain any functional PERV-C or -AC which encompasses selecting pigs whose genomes contain non-functional PERV-C or -AC but do not contain any functional PERV-C or -AC. This does not make sense because a pig that is “PERV-C and PERV-A/C negative” must have genomes that do not contain any functional or non-functional PERV-C or -AC. There should be a nexus with the preamble and the final pigs selected. Perhaps claim 1 should be limited to selecting pigs whose genomes do not contain any functional or non-functional PERV-C or -AC. Or perhaps applicants are attempting to say the genome of the pigs lack functional PERV-C or -AC, but may contain non-functional PERV-C or -AC. In that case, the pigs are not PERV-C or -AC “negative” as inferred by the preamble. Clarification is required.
Step c) of claim 1 requires sequencing the genome of the pigs obtained in step b), but this must have already occurred to provide pigs whose genomes have a total copy number of function and non-functional PERV between 4-40 using the method of Elliott. Clarification is required.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to use the method of claim 1 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. In particular, it is impossible to provide PERV-C and PERV-A/C negative pigs (preamble; step c) from pigs that have no “functional PERV-C and PERV-A/C” but may contain non-functional PERV-C or -AC as encompassed by the final step.
B) The specification does not enable “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. The specification and the art at the time of filing are limited to selecting pigs whose genomes contain a total copy number of functional PERV-A and PERV-B sequences between 1-10 for reasons set forth above. The specification does not correlate these limited steps to the broader embodiments of claim 2. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method of claim 2 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
C) The specification does not enable making any pigs whose genomes do not contain any PERV sequences that are capable of producing PERV particles as required in claim 4. The specification and the art at the time of filing are limited to selecting pigs whose genomes do not contain any functional PERV sequences for reasons set forth above. The specification does not correlate these limited steps to the broader embodiments of claim 4. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make any pigs as broadly encompassed by claim 4 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. In particular, it is impossible to provide PERV null pigs (claim 4) from pigs that have 4-40 copies of PERV-C and PERV-A/C (step a).
D) The specification does not enable making a pig whose genome does not contain any functional PERV-C and PERV-A/C as broadly encompassed by claim 5 for reasons set forth above.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
E) The specification does not enable using the method of claim 8 for reasons set forth in rejection A) if step a) of claim 8 is attempting to further limit the method of claim 1.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
F) The specification does not enable “(b) establishing a PERV-C and PERV-A/C negative cell line from the pigs of step (a); (c) gene editing cells of said cells of step (b) to eliminate or deactivate GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1 or SLA; (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 PERV-C and PERV-A/C negative pig 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 “gene-edited cell line”; however, the specification is limited to making a pig cell whose genome lacks any copies of PERV-C and PERV-AC for reasons set forth above.
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 “xenoantigen” 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 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. “eliminate or deactivate one or more xenoantigen genes”, 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 “eliminat[ing] or deactivat[ing] one or more xenoantigen genes” 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 “gene-edited cell line” 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 “eliminat[ing] or deactivat[ing] one or more xenoantigen genes” 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.
The oocyte in step f) may be “from a PERV-C and PERV-AC negative pig”, but the specification is limited to an oocyte whose genome lacks any copies of PERV-C and PERV-AC which is missing from the step. The pig may be a founder that does not have oocytes that lack any copies of PERV-C and PERV-AC; the oocyte in step f) MUST have a genome that lacks any copies of PERV-C and PERV-AC.
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.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to use the method of claim 8 as broadly written.
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 2 has been withdrawn in view of the amendment but still has an objection.
The rejection of claim 4 has been withdrawn in view of the amendment but still has an objection.
The rejection of claim 5 has been withdrawn in view of the amendment but still has an objection.
The rejection of claim 9 has been withdrawn in view of the amendment.
Pending rejections
A) Claim 1 is indefinite because the preamble of claim 1 requires “selecting PERV-C and PERV-A/C negative” pigs, step a) makes the distinction of pigs with total copy number of functional and non-functional PERV between 4-40, and the final step of claim 1 requires selecting pigs whose genomes do not contain any functional PERV-C or -AC which encompasses selecting pigs whose genomes contain non-functional PERV-C or -AC but do not contain any functional PERV-C or -AC. This does not make sense which makes the claim indefinite. A pig that is “PERV-C and PERV-A/C negative” must have genomes that do not contain any functional or non-functional PERV-C or -AC. There should be a nexus with the preamble and the final pigs selected. Perhaps claim 1 should be limited to selecting pigs whose genomes do not contain any functional or non-functional PERV-C or -AC. Or perhaps applicants are attempting to say the genome of the pigs lack functional PERV-C or -AC, but may contain non-functional PERV-C or -AC; however, the pigs are not PERV-C or -AC “negative” as inferred by the preamble. Clarification is required.
Step c) of claim 1 requires sequencing the genome of the pigs obtained in step b), but this must have already occurred to provide pigs whose genomes have a total copy number of function and non-functional PERV between 4-40 using the method of Elliott. Clarification is required.
Accordingly, the scope cannot be ascertained, and those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
B) The preamble of claim 8 does not have a nexus with claim 1. The final step of claim 8 requires pigs that are PERV-C and PERV-AC negative and “gene edited for one or more xenoantigens” but claim 1 is limited to pigs whose genomes do not contain any functional PERV-C and PERV-AC sequences. It is unclear whether the preamble bears patentable weight, therefore, it is unclear whether those of skill MUST select pigs whose genomes do not contain any functional and non-functional PERV- C and PERV-AC sequences or if pigs whose genomes do not contain any functional (but some non-functional) PERV- C and PERV-AC sequences will do.
The metes and bounds of “xenoantigens” in step c) selected from genes encoding GGTA1, CMAH,… …SLA of claim 8 does not make sense. The pig genes encode pig proteins; whether or not they induce an immune response in other species is irrelevant to the structure of the genes or the functions of the protein in the pig itself. 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. Pg 21, lines 11-17, discuss inactivating the GGTA1 (Examples 4 and 7), CMAH (Example 5), or both GGTA1 and CMAH (Examples 6 and 8) (Examples 4-8 on pg 33-43).
The phrase “to eliminate or deactivate [a GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1, or SLA gene]” in the phrase “gene editing the cells of the cell line to eliminate or deactivate [a GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1, or SLA gene] in step c) is an intended use and does not necessarily have to occur. And the breadth of “gene editing” is broad encompassing any insertion, deletion, or substitution that causes any functional change, leaves the function the same, or inactivates the function. The phrase ---inactivating an endogenous [GGTA1, CMAH, B4GALNT2, NEU5GC, ASGR1, or SLA gene] in a cell isolated from a pig selected in claim 1--- would be clear.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
C) Claims 16 and 17 remain indefinite for reasons set forth regarding claim 2 and are 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. Applicants’ argument is not persuasive. PCR MUST start with isolating genomic DNA. 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.
Applicants argue Elliott did not teach sequencing the entire genome of each pig. Applicants’ argument is not persuasive. Claim 1 does not require sequencing the entire genome of each pig. “Observ[ing] the number of copies of a particular nucleic acid sequence in the genome of an organism” as described by Elliott is “sequencing the genome of the pigs” as required in step c) of claim 1.
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 argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
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 argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
If attempts to reach the examiner are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on 571-272-2914.
The official fax number for this Group is (571) 273-8300.
Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638