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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09-04-2025 has been entered.
Applicant's listing of claims filed on 09-04-2025 have been received and entered. Claims 4, 9, 11, 13, 21, 23, 26, 30-32, 35-52, 55, 57, 59-60, 62 have been canceled. Claims 1-3, 5-8, 10, 12, 14-20, 22, 24-25, 27-29, 33-34, 53-54, 56, 58, 61 are pending in the instant application.
Applicant's listing of claims filed on 09-04-2025 has no new amendment. This is a Final rejection.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-3, 5-8, 10, and 12 in the reply filed on 10-09-2024 is acknowledged. The traversal is on the ground(s) that the search and examination of the Groups of claims does not present an undue burden on the Examiner. This is not found persuasive because Group I is directed to a method for producing a pathogen resistant porcine herd or population; Group II is directed to a method of enhancing the dissemination of improved growth performance traits in a porcine herd or population; Group III is directed to a method of increasing the number of female offspring in a porcine herd or population; Group IV is directed to a method for producing a high health porcine herd or population. There would be a serious search and examination burden because searching for sex-sorted sperm cell sample with different goals and criteria would not be applicable to another sex-sorted sperm cell sample. For examples, searching for sex-sorted sperm cell sample required different criteria for a pathogen-resistant porcine herd, for enhancing the dissemination of improved growth performance traits in a porcine herd, for increasing the number of female offspring in a porcine herd, or for producing a high health porcine herd. Therefore, they require employing different search queries in patent and non-patent literature.
The requirement is still deemed proper and is therefore made FINAL.
Claim 14-20, 22, 24-25, 27-29, 33-34, 53-54, 56, 58, 61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10-09-2024 .
Claims 1-3, 5-8, 10, and 12 are under consideration.
Priority
This application is US application filed on 10-14-2021 that claims priority from US provisional application no 63/092,299 filed on 10/15/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09-04-2025 are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Maintained - Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 8, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Waberski et al (Theriogenology 137 (2019) 2e7, Doi: 10.1016/j.theriogenology.2019.05.030, 31 May 2019) in view of Steen et al (Pub. No.: US 2014/0142421 A1, Pub. Date: May 22, 2014).
Regarding to claim 1, Waberski et al teach application of preserved boar semen for artificial insemination (title), and artificial insemination (AI) is now used for breeding more than 90% of the sows, and more efficient and sustainable pig AI awaits the introduction of sex-sorted sperm into AI practice (Abstract). Waberski et al teach CRISPR/Cas9 technology is now available to generate disease resistant boars as shown for the PRRS virus (Page 5, right column, 1st para.). Waberski et al teach semen used for routine AI: Traditional transcervical deposition of 70-100 mL extended semen containing between 1.5 and 2.5x109 sperm preserved for several days at 17oC continues to be the most common method of AI (Table 2) (Page 3, right column, 3rd para.).
Waberski et al teach Sex-sorted semen: Sex sorting continues to be based on the principle of DNA difference between the X and Y sperm which was originally developed for mammals and is known as the Beltsville Sperm Sexing Technology (Page 4, right column, 1st para.).
Waberski et al teach the sex-sorted sperm cell sample has a progressive motility of at least 60% in table 2 (in 11 pig breeding organization worldwide from A to K) (see table 2 on Page 4). Further, it is indicating that the progressive motility was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform sex-sorting semen a plurality of times out of the course of routine optimization to obtain “the sex-sorted sperm cell sample has a progressive motility of at least 60%” in order to use the viable sperm cells.
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Waberski et al teach sex-sorted semen (Page 4, right column, 1st para.). However, Waberski et al do not specifically teach at least 60% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes. Steen et al cure the deficiency.
Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). The invention relates to methods of using sex sorted semen from pure line boars of a Swine line in mating to increase the genetic merit of Swine at the level of commercial pig production ([0002], page 1). It should be understood that in certain embodiments of the invention, at least approximately 60%, 65%, 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of sperm cells in the subpopulation of sperm cells bear X chromosomes ([0014], page 2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Waberski et al by using methods for use of sex sorted semen to select at least 60% of the sperm cells in the sex-sorted sperm cell sample that carry X chromosomes as taught by Steen et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Steen et al provide explicit advantage of improving genetic management in swine (title) and increasing the genetic merit of Swine at the level of commercial pig production ([0002], page 1). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Steen et al were successful in using sex Sorted sperm cells to increase the genetic progress of a line ([0206], page 20).
Regarding to claims 8 and 12, Waberski et al teach CRISPR/Cas9 technology is now available to generate disease resistant boars as shown for the PRRS virus (Page 5, right column, 1st para.). Waberski et al teach semen used for routine AI (Page 3, right column, 3rd para.) and sex-sorted semen (Page 4, bridging left to right column).
Claims 2-3, 5, 10 are rejected under 35 U.S.C. 103 as being unpatentable over Waberski et al (Theriogenology 137 (2019) 2e7, Doi: 10.1016/j.theriogenology.2019.05.030, 31 May 2019) in view of Steen et al (Pub. No.: US 2014/0142421 A1, Pub. Date: May 22, 2014) as applied to claims 1, 8, 12 above, and further in view of Whitworth et al (Nat Biotechnol 34, 20–22 (2016). Doi:10.1038/nbt.3434, 7 December 2015).
The teachings of Waberski et al and Steen et al are as described above and are incorporated herein in their entirety. Waberski et al and Steen et al do not specifically teach female with one or more pathogen-resistant markers. However, Whitworth et al cures the deficiency.
Regarding to claim 2, Whitworth et al teach one founder male and one founder female, both of whom had mutations in exon 7 of CD163 (pathogen-resistant marker), were bred to produce offspring (Page 20, third column, 2nd para.). Since Waberski et al teach semen used for routine artificial insemination (Page 3, right column, 3rd para.) and sex-sorted semen (Page 4, bridging left to right column), it would have been prima facie obvious for a person of ordinary skill in the art to inseminate one or more females from the offspring with a sex-sorted sperm cell sample from a boar having one or more pathogen-resistant markers.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of routine artificial insemination with sex-sorted sperm cell of Waberski et al by using the offspring having one or more pathogen-resistant markers as taught by Whitworth et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Whitworth et al provide explicit advantage of using gene-edited pigs that are protected from porcine reproductive and respiratory syndrome virus (title). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Whitworth et al was successful in generation of pigs that are resistant to the PRRSV isolate NVSL 97-7895, a well-characterized, relatively virulent viral isolate that is commonly used in experimental PRRSV infection trials (Page 20, first column, 1st para.).
Regarding to claim 3 and 5, Waberski et al teach gene banking and acceleration of genetic progress at the nucleus and multiplier herd levels favor the use for frozen semen (Page 3, bridging left column and right column). Since Waberski et al teach routine artificial insemination (Page 3, right column, 3rd para.), a person of ordinary skill in the art would be motivated to use nucleus or multiplier herd for routine artificial insemination.
Regarding to claim 10, Whitworth et al teach one founder male and one founder female, both of whom had mutations in exon 7 of CD163 (pathogen-resistant marker), were bred to produce offspring (Page 20, third column, 2nd para.).
Claims 1-3, 5-8, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Prather et al (Pub. No.: US 2017/0035035 A1, Pub. Date: Feb. 9, 2017) in view of Steen et al (Pub. No.: US 2014/0142421 A1, Pub. Date: May 22, 2014) and Schenk (Pub. No.: US 2013/0137081 A1, Pub. Date: May 30, 2013).
Claim interpretation:
According to the specification of claimed invention, an "elite boar" is a boar produced in the genetic nucleus herd that has extremely high breeding value, such as superior genetic potential relative to the mean of the genetic nucleus herd population. Thus, "elite boar" is interpreted as a member of a genetic nucleus
Regarding to claim 1, Prather et al teach animals and cells have increased resistance to pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) , and the invention further relates to methods of breeding to create pathogen resistant animals and populations of animals made using such methods (Abstract) (For claim 1, the preamble).
Prather et al teach the methods of breeding, the fertilizing can comprise artificial insemination ([0325], page 28). Prather et al teach that for swine, mature oocytes can be fertilized in 500 µl Minitube PORCPRO IVF medium system with freshly-collected or frozen boar semen ([0236], page 21) (For claim 1, the claimed: inseminating one or more target sows with a sex-sorted sperm cell sample from a boar).
Prather et al teach frozen boar semen can be used for in vitro fertilization (IVF) ([0236], page 21). Prather et al provides genetically modified animals, offspring thereof, or animal cells comprising at least one modified chromosomal sequence in a gene encoding a CD163 protein ([0102], page 10) (For claim 1, the claimed: wherein the boar comprises one or more pathogen-resistant markers).
Prather et al provides a method of breeding to create animals or lineages that have reduced susceptibility to infection by a pathogen. The method comprises genetically modifying an oocyte or a sperm cell to introduce a modified chromosomal sequence in a gene encoding a CD163 protein into at least one of the oocyte and the sperm cell, and fertilizing the oocyte with the sperm cell to create a fertilized egg containing the modified chromosomal sequence in a gene encoding a CD163 protein ([0271], page 25) (For claim 1, the claimed: thereby producing offspring comprising one or more pathogen-resistant markers).
Prather et al does not teach sex-sorted sperm cell sample. However, Steen et al cures the deficiency. Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). The invention relates to methods of using sex sorted semen from pure line boars of a Swine line in mating to increase the genetic merit of Swine at the level of commercial pig production ([0002], page 1). It should be understood that in certain embodiments of the invention, at least approximately 60%. 65%, 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of sperm cells in the subpopulation of sperm cells bear X chromosomes ([0014], page 2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Prather et al by using sex sorted semen as taught by Steen et al, as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Steen et al provide explicit advantage of the improvement of genetic management of the line is the result of 1) increase of the genetic progress in the line and/or 2) improvement of the genetic dissemination (i.e., genetic merit of commercial product is closer to genetic merit at the genetic nucleus) ([0002], page 1). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Steen et al provides poof of principle for using sex sorted semen from pure line boars with working examples and data.
Prather et al does not teach the sex-sorted sperm cell sample has a progressive motility of at least 60%. However, Schenk cure the deficiency.
Schenk teach method of cryopreserving selected sperm cells (title). Schenk teach obtaining a selected sperm sample: Generally, the selected sperm sample contains normal, viable sperm. To this end, the ejaculate from which the sperm are obtained typically has at least about 50%, and preferably at least about 75% morphologically normal sperm. In these embodiments, generally at least about 40%, and preferably at least about 60% of the sperm in the ejaculate exhibit progressive motility ([0033], page 2). Schenk also teach that “the invention is exemplified herein with selection based on sex-type, and sex-selected sperm for use in the invention can be obtained using any selection strategy that takes advantage of slight differences in characteristics between X- and Y-type sperm …… describe selection based on differences in motility” ([0035], page 2), and FACS can be used for sex-selection of sperm because the X chromosome contains slightly more DNA than the Y chromosome ([0036], page 2), and the sperm were sorted on the basis of viability ([0108], page 8). Schenk also teach “Example 3 that describes a study of the effects of laser intensity and dye concentration of post thaw motility of sorted frozen sperm. This study indicates that the use of lower laser intensities during Sorting can increase post-thaw motility” ([0038], page 3). ”. Thus, it is indicating that the progressive motility was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform sex-sorting semen a plurality of times out of the course of routine optimization to obtain “the sex-sorted sperm cell sample has a progressive motility of at least 60%” in order to use the viable sperm cells.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Prather et al by obtaining at least about 60% of the sperm in the ejaculate exhibit progressive motility as taught by Schenk, as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Schenk teach that the selected sperm sample contains normal, viable sperm by selecting sample with at least about 60% of the sperm in the ejaculate that exhibit progressive motility ([0033], page 2). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Schenk teach that thawing yields viable sperm that can be used in procedures such as artificial insemination (AI) and in vitro fertilization (“IVF) ([0011], page 1) and Sperm were sorted on the basis of viability ([0108], page 8).
Regarding to claim 2, Steen et al teach inseminating one or more female swine in the one of the mating subtypes with the subpopulation of sperm cells ([0013], page 2). Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Steen et al teach male subgroup is defined by, or based on, one or more criteria including but not limited to, genetic merit (e.g., EBV) and genetic markers or mutations ([0013], page 2). Additionally, Prather et al teach the methods of breeding, the fertilizing can comprise artificial insemination ([0325], page 28). Prather et al teach frozen boar semen can be used for in vitro fertilization (IVF) ([0236], page 21). Prather et al provides genetically modified animals, offspring thereof, or animal cells comprising at least one modified chromosomal sequence in a gene encoding a CD163 protein ([0102], page 10) (For claim 2, the claimed: inseminating one or more females from the offspring with a sex-sorted sperm cell sample from a boar having one or more pathogen-resistant markers,).
Prather et al teach the modification in the chromosomal sequence in the gene encoding the CD163 protein reduces the susceptibility of the animal, offspring, or cell to infection by a pathogen (e.g., a virus such as PRRSV), as compared to the susceptibility of an animal, offspring, or cell that does not comprise a modified chromosomal sequence in a gene encoding a CD163 protein to infection by the pathogen ([0110], page 11) (For claim 2, the claimed: wherein the one or more pathogen-resistant markers from the boar and the one or more female offspring are the same or different).
Regarding to claims 3 and 5, Steen et al teach that in certain embodiments of the invention, the line, the male, the one or more female, and/or the progeny, may belong to or be members of a genetic nucleus, a daughter nucleus or a multiplier ([0013], page 2).
Regarding to claim 6, Prather et al teach methods of breeding to create pathogen resistant animals and populations of animals (Abstract). Prather et al provides non-human animals, offspring thereof, and animal cells that comprise at least one modified chromosomal sequence in a gene encoding a CD163 protein ([0010], page 2). Steen et al teach inseminating one or more female Swine in the one of the mating subtypes with the subpopulation of sperm cells ([0013], page 2) (For claim 6, the claimed: wherein the pathogen-resistant porcine herd or population is a pathogen-resistant female porcine herd or population).
Steen et al teach the male swine may belong to or be members of a genetic nucleus ([0013], page 2) (For claim 6, the claimed: wherein the boar is an elite boar).
Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Steen et al teach wherein at least 80% of sperm cells in the first subpopulation bear X chromosomes (page 15, right column, B7, [0186]). Thus, “at least 80%” as taught by Steen et al encompasses “at least 87%” as required by the claim. Steen et al teach the percentage of progeny that are female for each of the mating subtypes is between approximately 90 to 100% and the produced progeny are members of a daughter nucleus or a multiplier (page 17, right column, E12, [0186]) (For claim 6, the claimed: wherein at least 87% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes; and wherein about 65% to about 99% of the offspring are female, and the female offspring comprise the one or more pathogen-resistant markers). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to combine and modify the Prather et al and Steen et al inventions to provide about 65% to about 99% of the offspring are female carrying one or more pathogen-resistant markers in order to provide greater resistance to pathogens and survival rates within offspring, with reasonable expectation of success.
Regarding to claim 7, Steen et al teach inseminating one or more female swine in the one of the mating subtypes with the subpopulation of sperm cells ([0013], page 2). Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Steen et al teach male subgroup is defined by, or based on, one or more criteria including but not limited to, genetic merit (e.g., EBV) and genetic markers or mutations ([0013], page 2). Steen et al teach the male swine may belong to or be members of a genetic nucleus ([0013], page 2). Additionally, Prather et al teach the modification in the chromosomal sequence in the gene encoding the CD163 protein reduces the susceptibility of the animal, offspring, or cell to infection by a pathogen (e.g., a virus such as PRRSV), as compared to the susceptibility of an animal, offspring, or cell that does not comprise a modified chromosomal sequence in a gene encoding a CD163 protein to infection by the pathogen ([0110], page 11) (For claim 7, the claimed: inseminating one or more females from the offspring with a sex-sorted sperm cell sample from the elite boar having one or more pathogen-resistant markers, wherein the one or more pathogen-resistant markers from the elite boar and the one or more female progeny are the same or different)
Steen et al teach wherein at least 80% of sperm cells in the first subpopulation bear X chromosomes (page 15, right column, B7, [0186]). Thus, “at least 80%” as taught by Steen et al encompasses “at least 87%” as required by the claim (For claim 7, the claimed: wherein at least 60% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes).
Regarding to claim 8, Prather et al teach the pathogen preferably comprises a virus, e.g., PRRSV. For example, the modification can reduce susceptibility to a Type 1 PRRSV virus, a Type 2 PRRSV, or to both Type 1 and Type 2 PRRSV viruses ([0274]-[0275], page 25).
Regarding to claim 10, Prather et al teach a method of breeding to create animals or lineages that have reduced susceptibility to infection by a pathogen. The method comprises genetically modifying an oocyte or a sperm cell to introduce a modified chromosomal sequence in a gene encoding a CD163 protein into at least one of the oocyte and the sperm cell, and fertilizing the oocyte with the sperm cell to create a fertilized egg containing the modified chromosomal sequence in a gene encoding a CD163 protein ([0271], page 25).
Regarding to claim 12, Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Additionally, Prather et al provides genetically modified animals, offspring thereof, or animal cells comprising at least one modified chromosomal sequence in a gene encoding a CD163 protein ([0102], page 10).
Response to Arguments
Applicant's arguments filed 09-04-2025 have been fully considered but they are not persuasive.
1. Applicants argue that Waberski and Schenk do not teach or suggest the recited progressive motility of at least 60% in a sex-sorted sperm cell sample from a boar. Waberski's only reference to progressive motility is with regard to liquid preserved boar semen (not a sex-sorted boar semen sample), and the disclosure of Schenk upon which the Examiner relies (i.e., [0033]) for teaching a progressive motility of at least about 60% is with regard to a raw, unprocessed ejaculate from an unspecified species (not a sex-sorted boar semen sample) (remarks, page 9 – 10, item A).
Regarding to the remarks on page 11-14, item B, Applicants essentially argue that Waberski compares liquid boar semen preservation and frozen/cryopreserved boar semen, and Waberski extols the use of liquid semen for routine artificial insemination use. Raw semen is not equivalent to sex-sorted semen and Waberski does not teach or suggest that the values presented in Table 2 are in any way reflective of the progressive motility of sex-sorted semen. Waberski is completely silent as to sex-sorted semen: (i) Waberski discloses that the minimum standards for motility of raw semen is 70%; (ii) Waberski discloses that the threshold value for motility of extended/preserved semen is between 50% and 70%; (iii) Waberski as a whole is not consistent with the Office's analysis. At page 4 of Waberski, this section of Waberski is silent as to the motility of sexed semen. As noted above, there is no connection between Table 2 and the discussion of sex-sorted semen. Therefore, as a whole, Waberski does not teach or suggest that "the sex-sorted sperm cell sample has a progressive motility of at least 60%."
Response to Arguments:
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, it is noted that Waberski et al teach “Breeding organizations have defined individual thresholds for useable semen at 60-80% for motility” (abstract) and “a wider range of threshold values are reported for total motility, between 50 and 70% in preserved semen compared to raw semen” (Bridging last para. on right column page 3 to page 4), and Table 2 on page 4 teach minimum standards for the use of liquid preserved boar semen in 11 pig breeding organization worldwide with Progressive motility (%) of 70% and 80%. Thus, Waberski et al teach useable semen at 60-80% for motility at minimum standards.
Additionally, Waberski et al teach “Sex-sorted semen”: “Sex-sorting continues to be based on the principle of DNA difference between the X and Y sperm which was originally developed for mammals and is known as the Beltsville Sperm Sexing Technology. The original sorting method as developed for pigs was reported in 1991 by Johnson. Subsequent development of the process using a high-speed sorter made it more useful for low dose pig AI and insemination and/or with laparoscopy. Advances have continued in the commercial sector, with further improvement in sorting instrumentation, software and in the speed at which sperm can be sorted …… there is use of sexed pig semen in nuclear and multiplier herds by experimental delivery systems by Fast Genetics, in Canada” (Page 4, right column).
Taken together, Waberski et al teach minimum standards for progressive motility (%) of 60-80% to be usable semen and the use of “Sex-sorted semen” and “sexed pig semen”; thereby indicating that the progressive motility was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform sex-sorting semen a plurality of times out of the course of routine optimization to obtain “useable semen at 60-80% for motility” in order to use the “Sex-sorted semen”.
Applicants are picking, choosing, and mixing sections to formulate opinions that the prior arts do not teach sex-sorted sperm cell sample having a progressive motility of at least 60%. According to MPEP 716.01(c) (II), arguments by applicant cannot take the place of evidence: Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
2. Applicants argue that Waberski does not teach or suggest that the use of sex-sorted sperm in the pig industry is "routine" for artificial insemination. Rather Waberski discloses that "[t]he use of sex-sorted sperm in the pig industry is not yet developed for widespread use." See Waberski, page 3. As noted above, the Office is picking, choosing, and mixing sections (e.g., section 3.1 and Table 2) of Waberski to support the impermissible hindsight position to the exclusion of other parts (e.g., section 3.2) that are necessary for the full appreciation of what Waberski fairly suggests to one of ordinary skill in the art (remarks, page 15, item C).
Response to Arguments:
It is noted that Waberski et al further teach “Sex-sorting continues to be based on the principle of DNA difference between the X and Y sperm which was originally developed for mammals and is known as the Beltsville Sperm Sexing Technology. The original sorting method as developed for pigs was reported in 1991 by Johnson. Subsequent development of the process using a high-speed sorter made it more useful for low dose pig AI and insemination and/or with laparoscopy. Advances have continued in the commercial sector, with further improvement in sorting instrumentation, software and in the speed at which sperm can be sorted …… there is use of sexed pig semen in nuclear and multiplier herds by experimental delivery systems by Fast Genetics, in Canada” (Page 4, right column). Thus, Waberski et al provide evidence for using sex-sorted sperm for artificial insemination before the effective filing date of the rejected claims.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the Examiner has only relied upon what was known in the art via the teachings of the cited references (Waberski et al, Steen et al, and Whitworth et al).
3. Applicants argue that van der Steen does not cure the deficiencies of Waberski because van der Steen is silent regarding the sex-sorted sperm cell sample having a progressive motility of at least 60% (remarks, page 14). Whitworth does not cure the deficiencies of Waberski and van der Steen because Whitworth does not teach or suggest that the sex-sorted sperm cell sample has a progressive motility of at least 60% (remarks, page 15).
Response to Arguments:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Steen et al teach at least 60% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes. One of ordinary skill in the art would have been motivated to combine the prior arts because Steen et al provide explicit advantage of improving genetic management in swine (title) and increasing the genetic merit of Swine at the level of commercial pig production ([0002], page 1). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Steen et al were successful in using sex Sorted sperm cells to increase the genetic progress of a line ([0206], page 20). Whitworth et al teach female with one or more pathogen-resistant markers. One of ordinary skill in the art would have been motivated to combine the prior arts because Whitworth et al provide explicit advantage of using gene-edited pigs that are protected from porcine reproductive and respiratory syndrome virus (title). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Whitworth et al was successful in generation of pigs that are resistant to the PRRSV isolate NVSL 97-7895, a well-characterized, relatively virulent viral isolate that is commonly used in experimental PRRSV infection trials (Page 20, first column, 1st para.).
4. Applicants argue that Prather, van der Steen, and Schenk do not teach or suggest all elements of the claims. The Examiner has not established a prima facie case based on Prather, van der Steen, and Schenk because their combination does not teach or suggest all elements of the claims. In particular, Prather does not teach or suggest that: (1) the one or more target sows are inseminated with a sex-sorted sperm cell sample from a boar; (2) at least 60% of the sperm cells in the sexsorted sperm cell sample carry X chromosomes; and (3) the sex-sorted sperm cell sample has a progressive motility of at least 60%. (Remarks, page 16).
Response to Arguments:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case:
Prather et al teach methods of breeding to create pathogen resistant animals and populations of animals made using such methods (Abstract) (For claim 1, the preamble) that comprise artificial insemination ([0325], page 28), and for swine,([0236], page 21). Prather et al provides genetically modified animals, offspring thereof, or animal cells comprising at least one modified chromosomal sequence in a gene encoding a CD163 protein ([0102], page 10) (CD163 is pathogen-resistant markers).
Additionally, Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). The invention relates to methods of using sex sorted semen from pure line boars of a Swine line in mating to increase the genetic merit of Swine at the level of commercial pig production ([0002], page 1). It should be understood that in certain embodiments of the invention, at least approximately 60%. 65%, 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of sperm cells in the subpopulation of sperm cells bear X chromosomes ([0014], page 2). One of ordinary skill in the art would have been motivated to combine prior arts because Steen et al provide explicit advantage of the improvement of genetic management of the line is the result of 1) increase of the genetic progress in the line and/or 2) improvement of the genetic dissemination (i.e., genetic merit of commercial product is closer to genetic merit at the genetic nucleus) ([0002], page 1).
Further, Schenk teach method of cryopreserving selected sperm cells (title). Schenk teach obtaining a selected sperm sample: Generally, the selected sperm sample contains normal, viable sperm. To this end, the ejaculate from which the sperm are obtained typically has at least about 50%, and preferably at least about 75% morphologically normal sperm. In these embodiments, generally at least about 40%, and preferably at least about 60% of the sperm in the ejaculate exhibit progressive motility ([0033], page 2). Schenk also teach that “the invention is exemplified herein with selection based on sex-type, and sex-selected sperm for use in the invention can be obtained using any selection strategy that takes advantage of slight differences in characteristics between X- and Y-type sperm …… describe selection based on differences in motility” ([0035], page 2), and FACS can be used for sex-selection of sperm because the X chromosome contains slightly more DNA than the Y chromosome ([0036], page 2), and the sperm were sorted on the basis of viability ([0108], page 8). Schenk also teach “Example 3 that describes a study of the effects of laser intensity and dye concentration of post thaw motility of sorted frozen sperm. This study indicates that the use of lower laser intensities during Sorting can increase post-thaw motility” ([0038], page 3). ”. Thus, it is indicating that the progressive motility was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform sex-sorting semen a plurality of times out of the course of routine optimization to obtain “the sex-sorted sperm cell sample has a progressive motility of at least 60%” in order to use the viable sperm cells. One of ordinary skill in the art would have been motivated to combine prior arts because Schenk teach that the selected sperm sample contains normal, viable sperm by selecting sample with at least about 60% of the sperm in the ejaculate that exhibit progressive motility ([0033], page 2). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Schenk teach that thawing yields viable sperm that can be used in procedures such as artificial insemination (AI) and in vitro fertilization (“IVF) ([0011], page 1) and Sperm were sorted on the basis of viability ([0108], page 8).
5. Applicants argue that (i) van der Steen does not teach a person of skill in the art how to generate a sex-sorted semen having a progressive motility of at least 60%. van der Steen does not cure the deficiencies in the combination of Prather and Schenk because van der Steen does not teach or suggest all elements of the claims. In particular, as discussed above, van der Steen does not teach or suggest that the sex-sorted sperm cell sample has a progressive motility of at least 60%.
The Office asserts that "Applicant has not provided evidence for van der Steen is not enabling and does not provide a reasonable expectation of success." Applicant respectfully disagrees because MPEP § 2121 expressly provides that "[w]here a reference appears to not be enabling on its face ... an applicant may successfully challenge the cited prior art for lack of enablement by argument without supporting evidence" citing In re Morsa, 713 F.3d 104, 110 (Fed. Cir. 2013).
A person of ordinary skill in the art would not have arrived at the claimed process using the claimed sex-sorted sperm cell sample without undue experimentation because van der Steen does not teach a person of skill in the art how to produce a sex sorted sperm cell sample ……. For these reasons, van der Steen is not an enabling disclosure because arriving at the claimed invention would require undue experimentation (Remarks, page 16-17).
Response to Arguments:
Applicants have further engaged in selective reading of the teachings of Steen et al and attacking references individually where the rejections are based on combinations of references. Nevertheless, Steen et al teach “sorting a sperm cell sample from a male Swine in one of the mating subtypes into one or more subpopulations of sperm cells, wherein a majority of sperm cells in a subpopulation of sperm cells bear X chromosomes or Y chromosomes;” ([0013], page 2) and “genetic merit may be a function of based on, or determined by, the ability of sperm cells to be sex sorted and/or frozen based on the sperm cells viability, fertility, and/or motility after sorting and/or freezing, as well as a genetic marker for such a trait.” ([0015], page 2). Once the sperm cell sample is in the laboratory, various quality checks can be conducted on the sperm cell sample including checking the motility (e.g., via CASA System), viability (e.g., via flow cytometer), morphology (e.g., via microscopy) and concentration (e.g., via NucleoCounter) ([0147], page 10).
Additionally, as described above Schenk teach method of cryopreserving selected sperm cells (title). Schenk teach obtaining a selected sperm sample: generally, at least about 40%, and preferably at least about 60% of the sperm in the ejaculate exhibit progressive motility ([0033], page 2). Schenk also teach that “the invention is exemplified herein with selection based on sex-type, and sex-selected sperm for use in the invention can be obtained using any selection strategy that takes advantage of slight differences in characteristics between X- and Y-type sperm …… describe selection based on differences in motility” ([0035], page 2), and FACS can be used for sex-selection of sperm because the X chromosome contains slightly more DNA than the Y chromosome ([0036], page 2), and the sperm were sorted on the basis of viability ([0108], page 8). Schenk also teach “Example 3 that describes a study of the effects of laser intensity and dye concentration of post thaw motility of sorted frozen sperm. This study indicates that the use of lower laser intensities during Sorting can increase post-thaw motility” ([0038], page 3). One of ordinary skill in the art would have been motivated to combine prior arts because Schenk teach that the selected sperm sample contains normal, viable sperm by selecting sample with at least about 60% of the sperm in the ejaculate that exhibit progressive motility ([0033], page 2).
The examiner has cited reference above for prior arts’ enablement while applicants only provide opinions without any evidence. According to MPEP 716.01(c) (II), arguments by applicant cannot take the place of evidence: Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
6. Applicants argue that (ii) There is no reasonable expectation of success at arriving at the claimed invention based on the combination of Prather, van der Steen, and Schenk. There is no reasonable expectation of success in arriving at the claimed process based on van der Steen alone or in combination with Prather because van der Steen does not provide any hint, motivation, or suggestion to combine embodiments B7, and E12, which are cherry-picked by the Examiner to support the rejection. The Office asserts that a person of skill in the art would have been motivated to select process B and process E of van der Steen to support the obviousness conclusion. However, the Office has not explained why a person having ordinary skill in the art reading van der Steen would have been motivated to select process B and process E out of the 11 processes disclosed therein. van der Steen discloses eleven (11) processes of increasing the genetic progress or merits of an animal.
Having selected processes E and B, the Examiner has not demonstrated why a person of skill would selectively combine the process of B7 (out of B and B l-B22) with that of E12 (out of E and El-26) to arrive at the claimed methods.
The Office has not demonstrated how a person having ordinary skill in the art would have arrived at the claimed methods with a reasonable expectation of success solely by combining B7 and El2 with Prather when van der Steen does not provide any guidance on how to generate a sex-sorted sperm cell sample (Remarks, page 17-19)
Response to Arguments:
Applicant's arguments amount to nothing more than conjecture with mere allegations of patentability and lack of sufficient explanation or rationale. In this case, Steen et al teach processes E and B in [0186] stating that “Those of ordinary skill in the art will recognize that the invention described above includes many inventive embodiments, including at least the following: …. B. A method of increasing genetic merit of Swine comprising the steps of …... E. A method of increasing genetic merit of Swine…” ([0186], page 15-17). Thus, person of skill would use the process of B7 with that of E12 within [0186] to increase genetic merit of Swine because all are inventive embodiments that’s are all taught in a single paragraph [0186]. Further, Steen et al teach that “various quality checks can be conducted on the sperm cell sample including checking the motility (e.g., via CASA System), viability (e.g., via flow cytometer), morphology (e.g., via microscopy) and concentration (e.g., via NucleoCounter) ([0147], page 10). Thus, various quality checks such as calculation of subpopulation bear X or Y chromosomes or percentage of progeny that are female for each of the mating subtypes are routinely performed in the arts before the effective filing date of the rejected claims, and a person of skill would use teachings of Steen et al in [0186] as quality checks to increase genetic merit of Swine. One of ordinary skill in the art would have been motivated to do so because Steen et al provide explicit advantage of the improvement of genetic management of the line is the result of 1) increase of the genetic progress in the line and/or 2) improvement of the genetic dissemination (i.e., genetic merit of commercial product is closer to genetic merit at the genetic nucleus) ([0002], page 1). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Steen et al provides proof of principle for using sex sorted semen from pure line boars with working examples and data: Example 4 teaches preparation of sex sorted boar sperm cell samples (page 10-11), and Example 5 teaches cryopreservation of sex sorted boar sperm cell samples (Page 11-12), etc.
In summary, the Examiner cited a single paragraph [0186] to support the rejection and the scope of Steen et al ’s teachings in [0186] would be understood by those of ordinary skill in the art. Further, both items B. and E. in [0186] teach “A method of increasing genetic merit of Swine”; thus, those of ordinary skill in the art would use Steen et al’s teachings in [0186] to arrive at the claimed invention.
Applicants have not explained why a person having ordinary skill in the art reading van der Steen would not have been motivated to use process B and process E disclosed in a single paragraph of [0186]. Applicants have not demonstrated why a person of skill would not use the process of B7 with that of E12 in [0186] as taught by Steen et al.
7. Applicants argue that (iii) Schenk does not teach a person ofskill in the art how to generate a sexsorted sperm cell sample having a progressive motility of at least 60%. Schenk further discloses the progressive motility of raw semen to be at least about 60%. Paragraph [0033]. Specifically, Schenk states that "at least about 60% of the sperm in the ejaculate exhibit progressive motility." Indeed, at paragraph [0212], Example 7, Schenk discloses selecting ejaculates that have progressive motility> 60% because they are best for sorting. The sperm in the ejaculate of Schenk is equivalent to the raw semen described by Waberski, which is not equivalent to a sex-sorted sperm cell sample as claimed.
Schenk does not disclose, teach, or suggest a progressive motility of at least 60% for boar sex-sorted semen. Schenk only discloses progressive motility of bovine sperm, and at a percentage that reaches only 46%. Moreover, Waberski discloses that artificial insemination techniques used for cattle (bovine) were not directly applicable to pigs. Lastly, the minimum standards for raw semen motility was disclosed to be 70% in Waberski. However, Schenk discloses that the minimum for bovine is 60%. As such, Schenk is not enabling for porcine semen progressive motility because Schenk only discloses cattle/bovine applications. (Remarks, Page 19-20)
Response to Arguments:
Schenk teach method of cryopreserving selected sperm cells (title). Schenk teach obtaining a selected sperm sample: Generally, the selected sperm sample contains normal, viable sperm. To this end, the ejaculate from which the sperm are obtained typically has at least about 50%, and preferably at least about 75% morphologically normal sperm. In these embodiments, generally at least about 40%, and preferably at least about 60% of the sperm in the ejaculate exhibit progressive motility ([0033], page 2). Schenk also teach that “the invention is exemplified herein with selection based on sex-type, and sex-selected sperm for use in the invention can be obtained using any selection strategy that takes advantage of slight differences in characteristics between X- and Y-type sperm …… describe selection based on differences in motility” ([0035], page 2), and FACS can be used for sex-selection of sperm because the X chromosome contains slightly more DNA than the Y chromosome ([0036], page 2), and the sperm were sorted on the basis of viability ([0108], page 8). Schenk also teach “Example 3 that describes a study of the effects of laser intensity and dye concentration of post thaw motility of sorted frozen sperm. This study indicates that the use of lower laser intensities during Sorting can increase post-thaw motility” ([0038], page 3). ”. Thus, it is indicating that the progressive motility was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform sex-sorting semen a plurality of times out of the course of routine optimization to obtain “the sex-sorted sperm cell sample has a progressive motility of at least 60%” in order to use the viable sperm cells.
Applicants have further engaged in selective reading of the teachings of Schenk to state that “Schenk only discloses progressive motility of bovine sperm, and at a percentage that reaches only 46%.”. However, it is noted that Schenk’s evaluation of motility is for various different sperm samples under different conditions such as cooling, freezing etc. Even under these conditions, Schenk still can record several sperm samples with motility of 61% (see table 1, page 7) or 60% (see table 2, page 7).
Applicants have further cited Waberski et al reference in connection with Schenk to state that “Waberski discloses that artificial insemination techniques used for cattle (bovine) were not directly applicable to pigs.” ; however, it is notes that the Schenk reference is not used to modify Waberski et al reference. The Schenk reference is not used to modify Prather et al reference. Nevertheless, Waberski et al teach “Application of preserved boar semen for artificial insemination: Past, present and future challenges”(title). It is noted that boar is pig. Prather et al teach animals and cells have increased resistance to pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV)(abstract) and a porcine animal or offspring thereof or a porcine cell ([0109], page 10). Schenk reference teaches frozen sperm sample that includes porcine for artificial insemination or in vitro fertilization (Abstract). It is noted that porcine includes pig. Thus, all references are for pigs thereof which are enabling for porcine semen progressive motility.
As per MPEP 716.02, Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986), In the instant case, there is no evidence of record that selecting the sex-sorted sperm cell sample that has a progressive motility of at least 60% would lead to superior results over prior arts given that selecting sperm cell sample that has a progressive motility of at least 60% have been routinely performed in the arts.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632