DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 3/4/2026, claims 1, 6, 8, 11-12, 14, 18-21, 33 and 35-37 were pending.
In Applicant's Response filed on 6/26/2026, claim 1 was amended.
As such, claims 1, 6, 8, 11-12, 14, 18-21, 33 and 35-37 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of record of claims 1, 6, 8, 11-12, 14, 18-21, 33, and 35-37 under 35 USC §101 has been withdrawn in view of Applicant’s arguments.
Claim Rejections - 35 USC § 103
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 6, 8, 11-12, 14, 18-19, 21, and 36-37 remain rejected under 35 U.S.C. 103 as being unpatentable over Robl et al (US 8,551,705 B2, 28 Jan 2011; previously cited) as evidenced by IVF Glossary (Ovation Fertility, retrieved from the Internet 26 April 2025; previously cited) in view of Vichera et al (Reprod Fertil Dev. July 2011; 23(6):769-79).
Regarding claim 1 in-part and 18, Robl teaches a method for producing an animal embryo having a desired genetic makeup, the method comprising: (i) producing an animal embryo comprising a haploid genome of male or female origin (i.e., androgenetic or parthenogenetic), (ii) culturing said embryo to produce a multi-celled embryo comprising a haploid genome of male or female origin; (iii) isolating one or more cells from said multi-celled embryo and screening said one or more cells for a desired genetic makeup; (iv) selecting said one or more cells determined to comprise the desired genetic makeup; and (v) transferring the nucleus of said one or more cells selected in step (iv) into an oocyte and activating said oocyte to produce an embryo comprising said desired genetic makeup, where the embryo comprising the desired genetic makeup is diploid (see claim 2 and 16 of Robl).
Regarding claim 1 in-part and 11, Robl continues to teach that the male- or female-derived haploid cells are cultured to produce “propagating haploid cells” (Summary and Objects of the Invention” para 4). The oocyte is an enucleated or haploid oocyte (see claim 3 of Robl). The invention relates to the production and multiplication of cells containing haploid chromosome content and the use of these cells to produce an embryo with diploid content of DNA (col 4, lines 12-17).
Regarding claim 6 in-part, Robl teaches that suitable mammalian sources for oocytes include sheep, bovine, pigs, mice, human, etc. and will be obtained from primate or ungulates (col 10, lines 4-10). The animal embryo is produced by transfer of the nucleus of a parthenogenetic cell into an enucleated oocyte (see claim 11 of Robl).
Regarding claim 19 in-part, Robl teaches introduction of a selected male (i.e., androgenetic) or female haploid genome into an enucleated oocyte to produce a diploid cell (col 9, lines 40-47) and that the animal embryo is produced by fertilization of an oocyte that has removal of a male pronucleus therefrom (see claim 8 of Robl).
Regarding claim 21 and 36, Robl teaches that the selected haploid cells of male or female origin have their genomes introduced into a haploid oocyte and that the diploid nuclear transfer will be obtained wherein both the male and female DNA has been selected based on its genetic makeup (col 9, lines 40-50).
The teachings of IVF Glossary are relied upon in providing evidence that “multi-cell embryo” is defined as a cleavage stage embryo and states that an embryo is at the multi-cell stage from day 2 until day 4 when it develops into a morula (“Multi-cell Embryo” top of p. 3). Thus, absent evidence to the contrary, the multi-celled embryo of Robl is a pre-implantation embryo between cleavage and morula (>32 cells) stage (see also para 0025 of instant specification) and overlaps with “isolated from a preimplantation embryo up to and including the blastocyst stage” as in instant claim 1 in-part and “wherein the bovine embryonic haploid cell is isolated from a preimplantation embryo at cleavage, four cells, eight cells, or sixteen cells” as in instant claim 12.
Robl does not teach:
that the bovine androgenetic haploid embryo has been prepared by a method comprising removing an activated bovine oocyte’s genome either before or after fertilization of the oocyte by intracytoplasmic sperm injection of a single sperm.
Regarding (i), Vichera teaches comparison of the developmental ability of bovine androgenetic haploid embryos constructed by different methods, namely IVF and intracytoplasmic sperm injection (ICSI) before and after oocyte enucleation (abstract).
Vichera continues to teach that androgenetic haploid embryos were produced using four different strategies: (1) IVF before oocyte enucleation; (2) IVF after enucleation; (3) ICSI before oocyte enucleation; and (4) ICSI after enucleation. Once obtained, the blastomeres of these androgenetic haploid embryos were used as male genome donors to reconstruct biparental embryos by fusion with matured oocytes.
Regarding claim 18, Vichera teaches that to verify the cytoplasmic contribution of androgenetic haploid blastomeres, we used spermatozoa incubated previously with exogenous DNA that coded for a green fluorescent protein gene (pCX-EGFP) and the enhanced green fluorescent protein (EGFP)-positive androgenetic haploid blastomeres generated were fused with mature oocytes. Of the reconstructed embryos reaching the cleavage and blastocyst stages, 85.1% and 9.0%, respectively, expressed EGFP (P > 0.05). EGFP expression was observed in 100% of reconstructed embryos, with 91.2% exhibiting homogenic expression. To confirm sperm genome incorporation, androgenetic haploid blastomeres generated by ICSI prior to enucleation and using Y chromosome sexed spermatozoa were used for biparental embryo reconstruction. Incorporation of the Y chromosome was confirmed by polymerase chain reaction and fluorescence in situ hybridization analysis.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create diploid bovine embryos from embryonic haploid cells using the method as taught by Robl, where the bovine androgenetic haploid embryo is prepared by removing the oocyte genome before or after ICSI as taught by Vichera, to arrive at the instantly claimed invention. Vichera shows that haploid bovine embryos can be developed by ICSI (androgenetic). One of ordinary skill would have been motivated to apply the method as taught in Vichera in the method as taught by Robl to obtain the predictable result of having androgenetic haploid embryos that can be successfully used to develop diploid embryos as taught by the prior art.
Regarding instant claim 8, Vichera is silent to how many hours before or after fertilization the oocyte genome is removed. However, it would have been a matter of routine optimization using standard laboratory techniques available at the time of filing to determine the appropriate before or after fertilization to remove the genome of the oocyte as instantly claimed to create an androgenetic haploid embryo as taught by Vichera with a reasonable expectation of success. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). It might be good to include the optimization case law.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive.
On p. 9-10 of Remarks, Applicant argues that the amendment to claim 1 to include “an activated” bovine oocyte is sufficient to overcome the above applied rejections because Vichera does not purportedly remedy the deficiencies of Vichera. Applicant states that Vichera does not teach that the bovine oocyte’s genome is not removed before or after fertilization via ICSI. Applicant argues that Vichera does not teach activating a bovine oocyte before ICSI, and while it does teach activating after ICSI, it requires a separate chemical activation step using ionomycin.
While Applicant’s arguments have been fully considered, they are not persuasive. As Applicant concedes above, Vichera teaches that bovine oocytes can be removed once activated after ICSI, which is required by the instant claims. Applicant seems to be arguing that, because Vichera does not teach that the removal is before fertilization by ICSI, Vichera does not apply. However, the claim language recites these limitations in the alternative (i.e., removal before OR after fertilization is sufficient to meet the claim limitation). Moreover, Applicant’s argument regarding the use of ionomycin in Vichera is not commensurate in scope with the claims as the limitation is broad in scope and utilizes open-language “comprising.” As per MPEP 2111.03(I), the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("[L]ike the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended."). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) ("The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps."); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) ("Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp. v. CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("comprising" leaves "the claim open for the inclusion of unspecified ingredients even in major amounts"). Thus, Applicant’s arguments are not persuasive.
Claim(s) 14 remains rejected under 35 U.S.C. 103 as being unpatentable over Robl et al in view of Vichera et al as applied to claims 1, 6, 8, 11-12, 14, 18-19, 21, and 36-37 above, and further in view of American-International Charolais Association (Referenced herein as AICA; “Genomic Enhanced EPD” 23 Dec 2014; Retrieved from the Internet 26 Apr 2025 from https://charolaisusa.com/pdf/2015/GEPD_4c_hr.pdf; previously cited).
The teachings of Robl and Vichera were recited in the above 35 U.S.C. 103 rejection as applied to claim 1 of which claim 14 depends.
Regarding claim 14, Robl teaches that the haploid genome can be analyzed to detect the presence or absence of a specific DNA associated with a phenotype and that the screening for a desired genetic makeup (i.e., multiple traits) can be done by restriction fragment length polymorphisms analysis or single-strand conformational polymorphism analysis (see claims 19-20 of Robl).
Robl does not teach characterizing the genome of the haploid cells comprises screening and scoring the genome of the haploid cells to identify the presence or absence of polymorphisms indicative of commercially valuable traits.
AICA teaches that genetic evaluations can be sued to enhance selection and characterize genetics for animals for traits that impact profitability (p. 1, para 1). Genetic evaluations and genomic results are incorporated as a correlated trait (p. 1, para 2). Genetic correlation is calculated between the values obtained from the genomic testing results and phenotypic data. The stronger the genetic correlation, the more the genetic value will impact the EPD and accuracy for a trait. These traits include calving ease direct, birth weight, weaning weight, yearling weight, maternal milk, ribeye area, marbling, and scrotal circumference (p. 1, para 3). The test used to determine these traits examines 78,000 SNPs as well as proprietary SNPS for traits such as Horned/Poll, coat color, and genetic defects can be tested simultaneously as the data is produced (p. 2, “What is the merit” para 1). This shows that genetic traits in bovines can be scored through screening SNPs and renders obvious “scoring the genome . . . to identify the presence or absence of polymorphisms indicative of commercially valuable traits” as in instant claim 14.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to produce a diploid bovine embryo as taught by Robl and Vichera in combination, where the genome is scored based off of polymorphisms that indicate commercially valuable traits as taught by AICA, to arrive at the instantly claimed invention. As AICA shows that genetic evaluations can be performed on the genome of cows, one of ordinary skill would have been motivated to modify the method of Robl and Vichera in combination to include genome scoring as taught by AICA with a reasonable expectation of advantageously accurately selecting for traits such as birth weight, maternal milk, and marbling as taught by the prior art.
Response to Arguments
Applicant argues that AICA does not teach removing an activated bovine oocyte’s genome before or after ICSI fertilization. However, as previously stated above and conceded by Applicant, Vichera does teach activating bovine oocyte using ionomycin after ICSI then enucleation. Thus, Applicant’s arguments are not persuasive.
Claim(s) 20 and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Robl et al in view of Vichera et al as applied to claims 1, 6, 8, 11-12, 14, 18-19, 21, and 36-37 above, and further in view of Paffoni et al (Fertil Steril. 30 Oct 2006; 87(1):77-82; previously cited).
The teachings of Robl and Vichera in combination were recited in the above 35 U.S.C. 103 rejection as applied to claim 6 of which claim 20 depends.
Regarding instant claim 20 in-part, Robl teaches the introduction of the genome of the selected cell of (d) into an oocyte (see col 9 lines 40-55).
Regarding claim 35, Robl teaches that preimplantation genetic diagnosis can be performed on oocytes to diagnose single gene disorders by first polar body analysis and to identify oocytes that contain maternal unaffected genes (Background, para 4).
Neither Robl nor Vichera teach that the oocyte is parthenogenetically activated before maternal pronuclear formation.
Regarding claim 20 in-part, Paffoni teaches the in vitro development of human oocytes after parthenogenetic activation (title).
Paffoni continues to teach that oocytes were sequentially exposed to 5 uM ionomycin in IVF medium and after 18-20 hours, were evaluated for signs of activation (p. 78, para 7).
Paffoni continues to teach that oocytes showing one enlarged pronucleus and no extrusion of the second polar body were considered activated (same para). This shows that oocytes can be parthenogenetically activated before pronuclear formation.
Paffoni continues to teach that 70 of the embryos were then allocated to the ICSI procedure for fertilization (p. 79, Results, para 3). The treatment with ionomycin resulted not only in efficient oocyte activation, but also in parthenote development to the blastocyst stage (p. 80, Discussion, para 2).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create diploid bovine embryos from embryonic haploid cells using the method as taught by Robl and Vichera in combination, where the oocyte is parthenogenetically activated before pronuclear formation as taught by Paffoni, to arrive at the instantly claimed invention. Paffoni shows the successful parthenogenetic activation of human oocyte using ionomycin. One of ordinary skill would have been motivated to modify the method of Robl and Vichera to include parthenogenetic activation of the oocyte using ionomycin prior to introduction of the embryonic haploid cell into the oocyte as taught by Paffoni with the reasonably expectation of advantageously creating efficient oocyte activation and parthenote development to the blastocyst stage as taught by the prior art.
Response to Arguments
Applicant argues that Paffoni does not teach activating oocyte genome before ICSI and does not teach removing an activated oocyte’s genome before or after ICSI. However, as reiterated above, Vichera teaches that activated oocyte can have its genome removed after ICSI and Robl shows that selected haploid cells can be utilized in ICSI procedures. While neither Robl nor Vichera teach that the oocyte is parthenogenetically activated before pronuclear formation, Paffoni shows that parthenogenetic activation can be done via ionomycin for the purpose of efficient oocyte activation and parthenote development to the blastocyst stage. Thus, applicant’s argument is not persuasive.
Applicant further argues that the combination of Robl, Vichera, and Paffoni were identified using impermissible hindsight and that one of ordinary skill would not apply Paffoni to bovine oocytes. Applicant argues that Paffoni points out known differences in the success of activation for human parthenotes versus other species, including bovine, seep, and pigs.
While Applicant’s arguments have been fully considered, they are not persuasive. 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). Parthenogenetic activation of oocytes for efficient oocyte activation and parthenote development to the blastocyst stage was knowledge within the level of ordinary skill since at least 2006, well before the effective filing date of the instant invention.
The discussion section of Paffoni describes the use of additional agents to enable high activation and in vitro development rates in rhesus monkey, rabbit, bovine, sheep, and pig. It states that “[a]s opposed to what is observed in other species, human parthenotes often show low developmental competence, not progressing beyond the eight-cell stage” (p. 81, para 1). This comparison does not disparage parthenogenetic activation in bovines; rather it shows that there are differences between human and other animals (bovine included) and that parthenote development in humans is harder than in those other species. Thus, Applicant’s arguments are not persuasive.
Claim(s) 33 remains rejected under 35 U.S.C. 103 as being unpatentable over Robl et al in view of Vichera et al as applied to claims 1, 6, 8, 11-12, 14, 18-19, 21, and 36-37 above, and further in view of Prather (US 4,994,384 A, 27 Oct 1987; previously cited).
The teachings of Robl and Vichera were recited in the above 35 U.S.C. 103 rejection as applied to claim 1 of which claim 33 depends. The teachings will not be repeated here.
Neither Robl nor Vichera teach that the diploid embryo is cloned or multiplied to make multiple copies of the embryo.
Prather teaches a method for multiplying bovine embryos by enucleating a recipient oocyte, transferring the donor embryo nucleus into the enucleated recipient oocyte and fusing via dielectrophoresis to allow the generation of multiplied genetically identical cattle (abstract). The overall procedure may be described as cloning or as a multiplication of embryos for the production of multiple genetically identical embryos, and ultimately, animals (col 3, lines 48-52). The reference teaches that nuclear transplantation from a multi-cell embryo to a plurality of embryonic single cells offers the potential to overcome non—viability after two to four bisections and enable the production of large numbers of multiplied identical animals.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create diploid bovine embryos from embryonic haploid cells using the method as taught by Robl and Vichera in combination, where the diploid embryo is cloned or multiplied as taught by Prather, to arrive at the instantly claimed invention. Prather shows that bovine diploid embryos are capable of being multiplied or cloned by transferring the embryo nucleus into enucleated recipient oocytes. One of ordinary skill in the art would have been motivated to clone/multiply the resulting diploid embryos of Robl and Vichera in combination using a similar manner to the teachings of Prather with a reasonable expectation of advantageously creating multiple genetically identical embryos as well as use the clones in the production of large numbers of multiplied identical animals such as cattle as taught by the prior art.
Response to Arguments
Applicant argues that Prather does not teach removing an activated bovine oocyte’s genome before or after ICSI fertilization. However, as previously stated above and conceded by Applicant, Vichera does teach activating bovine oocyte using ionomycin after ICSI then enucleation. Thus, Applicant’s arguments are not persuasive.
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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/G.R./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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