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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04-21-2026 has been entered.
Applicant's amendments to the claims and arguments filed on 04-21-2026 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. Claim 63 has been added. Claims 1-3, 5-8, 10, 12, 14-20, 22, 24-25, 27-29, 33-34, 53-54, 56, 58, 61 and 63 are pending in the instant application.
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Claim 14-20, 22, 24-25, 27-29, 33-34, 53-54, 56, 58, 61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.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, 12 and 63 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 04-21-2026 and 08-03-2026 are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn- Claim Rejections - 35 USC § 103
Claims 1-3, 5-8, 10, 12 and 63 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 Van der 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). In view of applicant amendment to add claim 63 and upon conducting further prior art search and consideration, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below:
New and Maintained in modified form- 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 1-3, 5-8, 10, 12 and 63 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 Van der Steen et al (Pub. No.: US 2014/0142421 A1, Pub. Date: May 22, 2014) and Alkmin et al (Reproduction, Fertility and Development, 2016, 28, 556–564, Doi: 10.1071/RD14088, published online 28 August 2014).
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 do not teach 60% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes. However, Van der Steen et al cures the deficiency. Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title) and “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) and “ 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 Van der 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 Van der 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 Van der Steen et al provides poof of principle for using sex sorted semen from pure line boars with working examples and data.
Prather et al and Van der Steen et al do not teach the sex-sorted sperm cell sample has a progressive motility of at least 60%. However, Alkmin et al cure the deficiency.
Alkmin et al teach:
“Two experiments were conducted in boar semen samples to evaluate how both holding time (24 h) and the presence of seminal plasma (SP) before sorting affect sperm sortability and the ability of sex-sorted spermatozoa to tolerate liquid storage …. the quality (viability, total and progressive motility) and functionality (plasma membrane fluidity and intracellular generation of reactive oxygen species) of sex-sorted spermatozoa were evaluated after 0, 72 and 120 h storage at 15–17oC (10 ejaculates)” (see Abstract).
Experiment 2: “effects of SP and holding time on liquid storage of sex-sorted sperm: Sperm samples of 10 ejaculates from five boars (two per boar) that were randomly selected from boars whose ejaculates exhibited a well-defined split and showed optimal sorting efficiency in Experiment 1 were used. After sorting, the X- and Y-chromosome-bearing sperm samples were centrifuged at 3000g for 4 min at 21oC; the pellets were then diluted in BTS to a concentration of 20x106 spermatozoa mL-1 and stored in the liquid state at 15–17oC in a semen incubator (Nevera semen; 3tres3, Barcelona, Spain) for 120 h. Sperm quality and functionality were assessed after 0, 72, and 120 h storage” (Page 558, left column, 1st para).
Figure 4 shows a progressive motility of about 70% (after 0 h storage for all samples) and about 60% (after 72 h storage for 0% SP sample) (See Figure 4 page 561 and below)
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Additionally, in view of Alkmin et al’s teachings, 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 Alkmin 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 Alkmin et al stated that “the purpose of the present experimental study was to evaluate how extended holding of boar spermatozoa before sorting in the presence or absence of SP affects sperm sortability. In addition, the ability of the resulting sex-sorted spermatozoa to tolerate up to 120 h of liquid storage was evaluated” (Page 557, left column, 1st para.). Alkmin et al concluded that “a 24 h holding time before sorting did not negatively affect the efficiency of boar sperm sex sorting or the later ability of the sex-sorted spermatozoa to tolerate long-term liquid storage at 15–17oC. This attribute is particularly interesting for the dissemination of sex-sorted spermatozoa into the swine industry because it would allow boars housed in AI centers located far from sorting facilities to be included in sperm sex-sorting programs. The presence of a high proportion of SP in semen samples before sorting reduces the number of ejaculates per boar to be sorted and negatively influences the sperm sex-sorting efficiency, but does not affect the subsequent capability of sex-sorted spermatozoa to tolerate long-term liquid storage at 15–178C. These findings indicate the desirability of removing the SP after ejaculation in all boar semen samples subjected to the sorting process” (Page 563, left column, 2nd para.). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Alkmin et al were successful in performing sex-sorting for boar semen samples that tolerate long-term liquid storage at 15–17oC.
Regarding to claim 2, Van der 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). Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Van der 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, Van der 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 (pathogen-resistant marker) ([0010], page 2). Van der 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).
Van der 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).
Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Van der 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 Van der Steen et al encompasses “at least 87%” as required by the claim. Additionally, Van der 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 Van der 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, Van der 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). Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Van der 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). Van der 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)
Van der 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 Van der 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, Van der 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).
Regarding to claim 63, Alkmin et al teach “…After sorting, the X- and Y-chromosome-bearing sperm samples were centrifuged at 3000g for 4 min at 21oC; the pellets were then diluted in BTS to a concentration of 20x106 spermatozoa mL-1 and stored in the liquid state at 15–17oC in a semen incubator…” (Page 558, left column, 1st para.)
Additionally, Van der Steen et al teach “doses can vary in the range of or anywhere in between about 300x106, about 150x106, about 140x 106, about 100x106, about 70x106, about 50x106, or about 5x106 sex sorted sperm cells or less and can be administered into one or both uterine horns of a female Swine ([0024], page 3). The aforementioned doses can be administered in various volumes, including but not limited to 5 ml for every 150x106 sperm cells, or the same number of cells in a volume in the range of 5 ml, 10 ml, 15 ml, 20 ml, 25 ml, 30 ml or 100 ml, or somewhere between 5-10 ml, 10-20 ml, 20-30 ml, 30-40 ml, 40-50 ml, 50-60 ml, 60-70 ml, 70-80 ml, 80-90 ml or 90-100 ml ([0025], page 3). It is noted that, for example, 150x106 sperm cells in 6 ml is 2.5x 107 cells per milliliter. Furthermore, in view of the teaching of Van der Steen et al in [0024]- [0025] on page 3, it is indicating that the concentration of sex sorted sperm cells 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 use different concentrations of sex sorted sperm cells a plurality of times out of the course of routine optimization, in order to increase the effectiveness of inseminating a female swine to achieve fertilization without adversely impacting sperm cell health.
Claims 1, 8, 12 and 63 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 Van der 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 minimum standards for the use of liquid preserved boar semen in 11 pig breeding organization worldwide of 70%-80% of progressive motility (more than 60% progressive motility) in table 2 (in 11 pig breeding organization worldwide from A to K) (see table 2 on Page 4). 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.
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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. Van der Steen et al cure the deficiency.
Van der 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 Van der 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 Van der 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 Van der 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).
Regarding to claim 63 Van der Steen et al teach “doses can vary in the range of or anywhere in between about 300x106, about 150x106, about 140x 106, about 100x106, about 70x106, about 50x106, or about 5x106 sex sorted sperm cells or less and can be administered into one or both uterine horns of a female Swine ([0024], page 3). The aforementioned doses can be administered in various volumes, including but not limited to 5 ml for every 150x106 sperm cells, or the same number of cells in a volume in the range of 5 ml, 10 ml, 15 ml, 20 ml, 25 ml, 30 ml or 100 ml, or somewhere between 5-10 ml, 10-20 ml, 20-30 ml, 30-40 ml, 40-50 ml, 50-60 ml, 60-70 ml, 70-80 ml, 80-90 ml or 90-100 ml ([0025], page 3). It is noted that, for example, 150x106 sperm cells in 6 ml is 2.5x 107 cells per milliliter. Furthermore, in view of the teaching of Van der Steen et al in [0024]- [0025] on page 3, it is indicating that the concentration of sex sorted sperm cells 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 use different concentrations of sex sorted sperm cells a plurality of times out of the course of routine optimization, in order to increase the effectiveness of inseminating a female swine to achieve fertilization without adversely impacting sperm cell health.
Claims 2-3, 5, 6, 7, 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 Van der Steen et al (Pub. No.: US 2014/0142421 A1, Pub. Date: May 22, 2014) as applied to claims 1, 8, 12 and 63 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 Van der Steen et al are as described above and are incorporated herein in their entirety. Waberski et al and Van der 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 6, 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.). Additionally, Van der 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).
Van der 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).
Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Van der 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 Van der Steen et al encompasses “at least 87%” as required by the claim. Van der 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 Whitworth et al and Van der 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, Van der 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). Van der Steen et al teach methods for use of sex sorted semen to improve genetic management in swine (title). Van der 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). Van der Steen et al teach the male swine may belong to or be members of a genetic nucleus ([0013], page 2). Additionally, 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.). Thus, 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 an elite boar having one or more pathogen-resistant markers (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)
Van der 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 Van der Steen et al encompasses “at least 87%” as required by the claim (For claim 7, the claimed: wherein at least 87% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes).
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.).
Response to Arguments
Applicant's arguments filed 04-21-2026 have been fully considered but they are not persuasive. The teachings of Alkmin et al have been added to teach the limitation of “the sex-sorted sperm cell sample has a progressive motility of at least 60%” recited in claim 1 as described above. Relevant arguments for teachings of Waberski et al in view of Van der Steen et al and Whitworth et al are discussed below.
1 Applicants argue that
Table 2 of Waberski, as relied upon by the Examiner, does not relate to sex-sorted semen samples. Table 2 does not describe or relate to sex-sorted semen samples. Waberski clearly identifies the table as pertaining to the "[m]inimum standards for the use of liquid preserved boar semen in 11 pig breeding organization worldwide;" however, this in no way describes any actual semen samples, let alone any sex-sorted semen samples. Waberski, page 4. At most, Table 2 ofWaberski identifies desirous characteristics for porcine sperm samples for use in breeding but provides no teachings as to how to generate said samples, let alone sex-sorted samples with said characteristics. Furthermore, Waberski recognizes that "[t]he use of sex-sorted sperm in the pig industry is not yet developed for widespread use" in part due to anatomical challenges for artificial insemination in pigs and low yield and fertility. Id (emphasis added). Accordingly, Waberski not only fails to teach a sex-sorted porcine sperm cell sample having a progressive motility of at least 60%, it further recognizes the challenges associated with the achievement of a sex-sorted porcine sperm sample that is of an acceptable quality and directly refutes the Examiner's own assertion that "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." Office Action, page 4 (remarks, page 10-11).
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 application of preserved boar semen for artificial insemination (title), and the use of 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 teach “Minimum standards for the use of liquid preserved boar semen in 11 pig breeding organization worldwide” with 70% to 80% of progressive motility in table 2 on page 4 (in 11 pig breeding organization worldwide from A to K) (see table 2 on Page 4). 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. Waberski teach that the use of sex-sorted sperm in the pig industry have been invented and available to public see Waberski teaching in page 4 (below). Applicants’ arguments regarding to “the use of sex-sorted sperm in the pig industry is not yet developed for widespread use…..due to anatomical challenges for artificial insemination in pigs and low yield and fertility” are not persuasive because there is no evidence in record to prove that these challenges with the use of sex-sorted sperm would be not achievable or prevent a person of ordinary skill in the art to achieve a progressive motility of more than 60% in view of using “Minimum standards for the use of liquid preserved boar semen in 11 pig breeding organization worldwide” as taught by Waberski et al above.
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2 Applicant cited Spinaci et al for the arguments:
Spinaci et al. (Theriogenology, 85:65-73 (2016); "Spinaci," a copy of which is provided for ease of reference) further rebuts the Examiner's assertion of routine optimization. Spinaci teaches that "the use of sexed semen in the swine industry is far from being a routine procedure." Spinaci, page 65, first column (emphasis added). As discussed in section 2.2 of Spinaci ("Damage to boar spermatozoa during sorting"), sex-sorting causes damage to cells from "chemical, physical, and electrical insults," which can kill cells and damage the surviving cells to such an extent that viability and fertility are greatly reduced. Id at page 66, second column. Sample storage represents an additional challenge to commercial applications of sex-sorted porcine sperm, as "cryopreservation leads to a boar-dependent impairment of sperm parameters such as motility, viability, malondialdehyde generation, and DNA fragmentation." Id at page 67, second column (See also section 3 of Spinaci: "Storage of sexed boar semen is necessary to ship it from sorting facilities to recipient females for use on a wider scale." Id. at pages 66-67) (emphasis added). Spinaci concludes that:
More than 20 years after the production of the first litters of pigs from sexed semen, the application of sex sorting in the porcine production system still presents several major challenges. Many efforts have been made to increase the sorting efficiency in terms of yield and sperm quality.
Spinaci and Waberski both serve to directly rebut the Examiner's assertion that arriving at the claimed elements would be mere routine optimization. Indeed, methods of producing sexsorted porcine sperm with sufficient viability and motility for implementation represents a long-felt but unmet need in the art, and not merely an opportunity for routine optimization as asserted by the Examiner. A person having ordinary skill in the art would not have had a reasonable expectation of success in practicing the claimed methods in view of Spinaci's description of the repeated failure by others in attempting to generate sex-sorted porcine sperm samples, let alone sex-sorted porcine sperm samples in which at least 60% of the sperm cells in the sex-sorted sperm cell sample carry X chromosomes, and in which the sex-sorted sperm cell sample has a progressive motility of at least 60% (remarks, page 11-12).
Response to arguments:
Applicant cited Spinaci et al. (2016) “the use of sexed semen in the swine industry is far from being a routine procedure”. However, it is noted that Spinaci et al. made no mention that sex-sorting procedure would not result in at least 60% for motility. The review of Spinaci et al. mentioned several difficulties but also acknowledge and provide proof of principle for using sexed sorted semen that is not new in the industry. It appears applicant’s opinion is directed to that there had been no success before the affective filing date of the claimed invention to achieve useable semen at least 60% for motility after sex-sorting procedure, and there is no motivation to optimize to achieve at least 60% for motility after sex-sorting procedure. In this case, it is noted that Waberski et al (in 2019) 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 motivation for using semen at 60-80% for motility at minimum standards with Artificial insemination (AI) for the use of sexed sorted semen.
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”.
3 Applicants argue that:
The Examiner characterizes van der Steen as teaching "methods for use of sex sorted semen to improve genetic management in swine." Final Office Action, page 5. However, van der Steen is completely silent as to the progressive motility of the sex-sorted samples. Furthermore, van der Steen is merely a prophetic disclosure that provides no data characterizing sex-sorted porcine sperm generated using the methods disclosed therein. See van der Steen at Examples 4-5. A person of ordinary skill in the art at the time of filing would have viewed the methods of generating sex-sorted porcine sperm described in van der Steen as little more than a set of experimental plans with desired outcomes and would have had little confidence if any that the methods could be successfully implemented in view of the negative teachings of Spinaci (Remarks, page 13)
Response to arguments:
It is noted that van der Steen et al teach:
“methods of increasing genetic merit of swine by establishing a plurality of mating subtypes for a line of swine, and determining a percentage of progeny that are male for each of the mating subtypes, or a percentage of progeny that are female for each of the mating subtypes, that would result, relative to a control, in an increase in genetic merit in the line; the invention further relates to 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” (Abstract).
“In a further embodiment, 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).
Example 4: Preparation of Sex Sorted Boar Sperm Cell Samples (page 10-11): “Once the sex sorted sperm cell sample has been obtained, it can be used with conventional artificial insemination procedures, such as intra-cervical insemination, in vitro fertilization or artificial insemination with deep intrauterine catheter or laparoscopy” ([0157], page 11).
Example 5 cryopreservation of sex sorted boar sperm cell samples (page 11-12): “After sorting, the 50 ml tubes containing the sex sorted sperm cells (with 20 million cells) can be divided into tubes of 15 ml …” ([0159], page 11), and “…The motility of the sperm cells can then be checked. If acceptable, the tubes can be taken to a programmable temperature control machine…” ([0160], page 11).
Thus, the technique of sex-sorting of boar sperm was taught before effective filing dating of the claim invention, and the viability and/or motility after sorting was recognized in the prior art to be a result-effective variable.
Conclusion
No claim is allowed.
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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