DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 10-11, 13-15 and 28-29 are pending.
Claims 10-11, 13-15 and 28-29 are under examination.
New Claim Objections
Claim 10 is objected to because of the following informalities:
Claim 10 recites “thereby producing a cell or embryo” in the thereby clause. While it is clear this is a Bos taurus cell or embryo from the preamble, it is recommended that Applicant amend to indicate the cell or embryo produced is a Bos taurus cell to increase the clarity. This could be done as “thereby producing a Bos taurus cell or embryo.”
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112(a)
The rejection of claims 32-33 and 35-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement because the amendment filed on 17th, March, 2025 contained limitations that appeared to be new matter is withdrawn in view of the cancellation of these claims.
Claim Rejections - 35 USC § 112(a)
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10-11, 13-15, 28-29, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the amendment filed on 2nd, December, 2025 claim 10 was amended to remove the following limitations:
“which produces a truncation of the transcript or protein expressed from the prolactin receptor (PRLR) gene” and
thereby producing a cell or embryo “capable of generating a Bos taurus animal which has an increased tolerance to heat, an increased resistance to ticks, and/or a desirable coat texture which comprises at least one selected from the group consisting of a thin coat, a light coat, a sleek coat, and a short coat, relative, respectively, to the tolerance to heat, the resistance to ticks, and the coat texture in a Bos taurus animal that does not carry the one or more alterations in the genomic DNA”
As presently claimed, the removal of these recited limitations substantially broadens the claims because the claims now encompass all results and uses of the methods and further the claims now encompass the method in vivo in Bos taurus cell.
The removal of these limitations, which broadens the scope of the claims as discussed above appears to be new matter because Applicant’s disclosure does not support the broader claim for the reasons stated below.
A review of the originally filed specification by the Examiner did NOT find any explicit basis for the broader method as claimed without the recited limitations. The disclosure (including the specification, claims and sequence listing) as originally filed, does not contain an explicit recitation of the broader claim as presently claimed.
Regarding explicit, implicit or inherent support, the closest support for these limitations is the disclosure of a method for generating an animal which is more likely than not to have an increased tolerance to heat, an increased resistance to ticks, and/or a desirable coat texture, the method comprising at least the step of introducing one or more genetic alteration to the PRLR gene of one or more cell used to generate the animal. In a related aspect, the invention also provides a method for generating one or more cells which may be of use in generating an animal which is more likely than not to have an increased tolerance to heat, an increased resistance to ticks, and/or a desirable coat texture, the method comprising at least the step of introducing one or more genetic alteration to the PRLR gene of one or more cell where the one or more genetic alteration includes a deletion of a C at the position corresponding to position 39136559 on chromosome 20 of Bos Taurus (pg. 25).
The disclosure of this narrower method with a specific result does not provide support for all possible results and uses of the method as claimed and further does not provide support for embodiments of methods of editing in vivo which are encompasses by the amended claims.
As noted by MPEP 608.04(a), new matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method.
In the instant case one skilled in the art would NOT consider the full genus gene editing methods with all possible results or uses as well as in vivo embodiments to be explicitly, implicitly, or inherently supported by Applicant’s disclosure.
Hence, there is insufficient written descriptions support for the instantly claimed limitation of and Applicant has not shown possession of the invention.
Response to Remarks
Applicant states “The features of claim 32 have been incorporated into claim 1” and “No new matter has been added” (pg. 4).
In response, previous claim 32 does not provide support for the full genus gene editing methods with all possible results or uses as well as in vivo embodiments which are encompassed by instant claims as amended.
For the issues discussed above, Applicant has not provided the location of support for this amendment. When filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure.") The claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported (see MPEP 2163 (I)), and therefore the claims are rejected under 35 U.S.C. 112(a) above as failing to comply with the written description requirement.
Withdrawn Claim Rejections - 35 USC § 112 (a)
Enablement
The rejection of claims 32-33 and 35-37 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph as failing to comply with the enablement requirement as set forth in the previous office action is withdrawn in view of the cancellation of these claims.
Claim Rejections - 35 USC § 112 (a)
Enablement
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10-11, 13-15, 28-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Wands Factors
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
Nature of the Invention and Breadth of the Claims
Instant claims encompass:
Methods of producing a Bos taurus cell or embryo comprising deleting a single nucleotide consisting of a cytosine (C) at position 39136559 of chromosome 20 of Bos taurus thereby producing a cell or embryo (claim 10 and dependents)
The broadest reasonable interpretation of the scope of this genus includes:
“a Bos taurus cell”
this includes all possible Bos taurus cells including cells in vivo
“deleting a single nucleotide consisting of a cytosine (C) at position 39136559 of chromosome 20 of Bos taurus”
This includes all possible method steps to delete the single nucleotide which includes:
all possible gene-editing technologies such as but not necessarily limited to CRISPR Cas systems with all possible guide RNAs and targets as well as Zinc finger nucleases meganucleases or TALENs with all possible targets
all possible vector types such as but not necessarily limited to viral (such as AAV or lentiviral vectors) and non-viral vectors (such as liposomes or LNPs)
Direction or Guidance Presented
While contemplating methods of producing a Bos taurus cell or embryo the method comprising deleting a single nucleotide consisting of a cytosine (C) at position 39136559 of chromosome 20 of Bos taurus Applicant provides limited guidance on using a gene editing technology to make the deletions. Specifically, Applicant merely contemplates making the claimed deletion (pg. 25), and Applicant generally describes and contemplates methods of gene editing in a prophetic example (Example 5). Applicant does not provide any additional active method steps, or any guidance for specific targets for a gene editing method. Applicant provides no guidance for a gRNA for CRISPR methods and Applicant provides no guidance for targets for Zinc finger nucleases, meganucleases, or TALENs or any other gene editing method. The only guidance provided by Applicant is the location of the deletion.
Furthermore, the information in the prophetic example is drawn to embryos only and there is no guidance for editing other cells of Bos taurus or editing in vivo which is encompassed by instant claims.
Present Working Examples
Prophetic Example 5
Production of Animals Using Gene-Editing (pg. 76-77)
In prophetic Example 5, Applicant generally describes and contemplates methods of gene editing. There is no reduction to practice. There is no specific targeting sequence or specific nuclease contemplated.
In summary, Applicant provides the following general prophetic guidance:
Embryos are generated by IVF
one or more genetic alteration in the PRLR gene, for example those which result in an increase in the activity of PRLR, are identified
Applicant specifically cites “mutations that will truncate the protein produced by the long-form of the PRLR gene to a length of 461 amino acids in cattle” as one embodiment.
mutations may consist of a single base deletion, as in the Senepol 'slick' mutation, a single base addition, or may be more complex producing a stop codon at the desired position in the PRLR gene.
Applicant cites the art for gene editing methods (“gene editing tools will be used (such as those described in Wang et al., 2013 and Wenfang et al., 2013) to introduce the desired base change(s) to the PRLR gene in a zygote”).
Importantly, this Example is prophetic.
Applicant does not cite a specific nuclease, a specific target or specific components or sequences of the nuclease sequence to be used. These elements are required for one of ordinary skill to reasonably be able to perform the claimed method. The art cited by Applicant (Wang et al., 2013 and Wenfang et al., 2013) are drawn to entirely different methods of editing entirely different regions of the genome and do not enable a specific method of editing a specific region of the Bos taurus genome in an embryo or in an in vivo or in vitro cell.
Absent Working Examples
Importantly, the specification provides broad and non-specific guidance, and the specification does not provide a working example of using a gene-editing technology to make a specific deletion of a single nucleotide consisting of a cytosine (C) at position 39136559 of chrornt1some 20 of Bos taurus.
The specification does not provide guidance or a working Example with a specific nuclease, specific spacer sequences, or specific targets to obtain the desired mutation.
State of the Art and Unpredictability of the Art
Editing the Genome
Regarding generally editing the genome, Applicant is directed to the art of Gaj et al. (Trends Biotechnol. 2013 May 9;31(7):397–405.; see IDS filed 6th, August, 2020; henceforth “Gaj”). Gaj generally describes the state of the art for gene editing with ZFN, TALEN, and CRISPR Cas in July, 2013, before and around the effective filing date of the claimed Application. Gaj also describes the state of the art for targeted gene inactivation via homologous recombination and knockdown by RNAi (pg. 1 last para. and pg. 2 1st para.). All of these gene editing types and more are encompassed by Applicant’s claims. Gaj evidences that the state of the art before and around the effective filing date of the claimed invention is unpredictable for the reasons stated below.
Targeted Gene Inactivation via Homologous Recombination
Specifically, regarding targeted gene inactivation via homologous recombination, Gaj evidences the use of this technique has been hampered by several factors, including the low efficiency at which engineered constructs are correctly inserted into the chromosomal target site, the need for time-consuming and labor-insensitive selection/screening strategies, and the potential for adverse mutagenic effects (pg. 1 last para. and pg. 2 1st para.). Therefore, because targeted gene inactivation via homologous recombination requires time-consuming and labor-insensitive selection/screening strategies which have not been disclosed by Applicant, the result of this method is unpredictable, and Applicant is not enabled for targeted gene inactivation via homologous recombination.
Targeted gene knockdown by RNA interference (RNAi)
Regarding targeted gene knockdown by RNA interference (RNAi), Gaj evidences this is unpredictable because it is incomplete, varies between experiments and laboratories, has unpredictable off-target effects, and provides only temporary inhibition of gene function. These restrictions impede researchers’ ability to directly link phenotype to genotype and limit the practical application of RNAi technology.
ZFN’s, TALENs and CRISPR
Regarding ZFN’s, TALENs and CRISPR, although Gaj teaches these methods have expanded the ability to manipulate and study model organisms (Future Directions, pg. 6 last para.), Gaj teaches to achieve the full potential of this technology, many important questions and challenges must be addressed (Future Directions, pg. 6 last para.’ Box 3).
Specifically, Gaj evidences the following limitations:
Several limitations of targeted nucleases are driving the development of alternative types of programmable enzymes for genome engineering. For example, off-target effects created by site-specific nucleases can be toxic to cells, and difficult to comprehensively predict and monitor. Additionally, because targeted nucleases rely on non-homologous end joining (NHEJ) and homology-directed repair (HDR) to induce genetic alterations, this technology may be limited by the availability of the desired DNA
repair mechanism in particular cell types (Box 1).
In order for recombinases and transposases to achieve the level of general
utility afforded by site-specific nucleases, significant improvements in their performance
and flexibility are needed (Box 1).
Although site-specific nucleases provide a means for introducing diverse custom
alterations at specific genomic locations, this technology is still limited by methods for
delivering these enzymes into relevant cell types (Box 2).
Further, regarding ZFN’s, TALENs and CRISPR, these systems each have requirements for design for specific locations, with some locations unable to be specifically targeted. For examples, Gaj evidences that the TALE binding site should start with a T for TALEN systems (pg. 3 last para.), and that CRISPR systems require a specific PAM site (pg. 6 2nd para.).
Finally, Gaj evidences the state of the art before and around the effective filing date of the claimed invention leaves outstanding questions of the effectiveness of ZFNs and TALENs, best methods for delivering site-specific nucleases into cells, as well as specificity and safety of CRISPR/Cas9 (Box 3).
In sum, Gaj evidences that although ZFN’s, TALENs and CRISPR have potential, they are still unpredictable due to issues in effectiveness, specificity, delivery of the systems, and safety. Therefore, because ZFN’s, TALENs and CRISPR were not predictable as of the effective filing date of the claimed invention, Applicant is not enabled for these gene editing methods.
Gene-editing in Livestock
TALENs and ZFN
Regarding the gene editing methods in Livestock, Applicant is directed to the art of Carlson et al. (Proc Natl Acad Sci U S A . 2012 Oct 23;109(43):17382-7.; see IDS filed 6th, August, 2020; Epub 2012 Oct 1.; henceforth “Carson”). The disclosure of Carl evidences gene editing in livestock was unpredictable as of the effective filing date of the instant Application. Specifically, Carlson evidences zinc-finger Nucleases are unpredictable due to technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget (abstract and pg. 17382 col. 2).
Further, Carlson evidences that TALEN nucleases are unpredictable in livestock for use in the creation of an embryo. Specifically, Carlson teaches development was significantly impaired in conditions with the greatest indel frequency (pg. 17383 col. 1), and only one-third of pig zygotes cytoplasmically injected with the TALEN/EGFP mRNA fluoresced at a detectable level (pg. 17386 col. 1). Carlson also evidences an alternative method of homologous recombination in primary fibroblasts followed by somatic cell nuclear transfer, but this was inefficient and the length of time for gestation and reproductive maturation for livestock represent significant barrier to homozygous gene inactivation or the engineering multiple loci (p.17382, col 1, par 1).
Additionally, the gene editing methods of the art require specific targeting elements designed to target specific sequences, as well as specific donor sequences, if applicable. The art of Carlson evidences precise genome editing of a specific region using precisely designed pairs of TALENs (pg. 17382 col. 2). The art of Carlson teaches that each of the TALENs revealed three unique indels (Figure 1). In other words, even for similarly designed TALENs, with similar target regions, different genetic alterations (unique indels) resulted from the gene editing.
Moreover, Carlson evidences ZFN based strategies are limited by target sites (pg. 17382 col. 2), indicating that careful design is required based on the gene editing and nuclease system used, and some systems may not even be able to be designed for the desired mutation. Accordingly, specific target regions, nuclease types and target elements and sequences are required to enable one of ordinary skill in the art to make and use the invention.
Regarding TALEN gene editing methods, which are encompassed by all claims and are specifically recited in claim 13, Applicant is directed to the post-art of Wu et al. (Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):E1530-9. Epub 2015 Mar 2.; henceforth “Wu”). Wu specifically evidences that after and around the effective filing date of the claimed invention, TALEN gene editing methods were unpredictable. Specifically Wu evidences TALEN induces a double-strand break (DSB) at a precise, defined position in the genome, resulting in unpredictable gene mutations when the DSBs are repaired erroneously by nonhomologous end joining (NHEJ) (pg. E1520 col. 1 1st para.).
Therefore, because TALEN and ZFN gene editing methods were not predictable in Livestock Applicant is not enabled for these gene editing methods.
Further, regarding ZFNs, Applicant is directed to the art of Yu et al. (Cell Res. 2011 Nov;21(11):1638-40. Epub 2011 Sep 13.; henceforth “Yu”).Yu evidences that targeting of a specific mutation with ZFNs in cattle is unpredictable. Specifically, Yu specifically designed 3 ZFNs of which, only 1 of the 3 cut at the intended target cite (Set 2 cut only 1/101 times and Set 3 cut 0/159 times). Therefore, Yu evidences that gene editing of a specific target in cattle in unpredictable because successful cutting of a target location with a ZFN is does not always work even when precisely designed.
Therefore, because ZFN gene editing methods were not predictable in Cattle, Applicant is not enabled for these gene editing methods.
CRISPR
Regarding CRISPR gene editing methods, which are encompassed by all claims and are specifically recited in claim 13, Applicant is directed to the post-art of Heo et al. (Stem Cells Dev. 2015 Feb 1;24(3):393-402. Epub 2014 Nov 3.; henceforth “Heo”). Heo specifically evidences the state of the art after the effective filing date of the claimed invention was not routine or conventional and therefore was unpredictable. Specifically, Heo evidences “reliable tools for gene targeting in livestock, are still inefficient, and thus not routinely used” (abstract). Heo further evidences that after the effective filing data of the claimed invention that “genetic engineering is plagued with several serious limitations that affect the production of transgenic livestock” and “conventional techniques that involve gene targeting by homologous recombination in somatic cells have proved to be difficult” and “the length of time required to generate livestock represents a significant barrier to the homozygous inactivation of a gene or engineering of multiple loci” (pg. 393 1st para.). Heo further evidences gene editing of cattle after the effective filing date was unpredictable by reciting that “it remains to be determined whether the same strategy could be applied to the genomes of livestock, specifically cattle, which can be used to generate transgenic animals” (pg. 393 1st col. 1st para.).
Lastly, Heo specifically evidences gene editing of bovine embryos using CRISPR-Cas9 had not occurred until after the filing date of the claimed invention (pg. 400 col. 1 “this study demonstrates for the first time successful gene knock-in in bovine embryos using CRISPR/Cas9 nuclease”).
Therefore, because CRISPR-Cas gene editing methods in cattle were unpredictable, and had not been successful until after Applicant’s effective filing date, Applicant is not enabled for these gene editing methods.
Single Nucleotide Editing
Applicant’s claim encompasses a single nucleotide editing. Applicant is directed to the post- filing art of Ochiai et al. (Int J Mol Sci . 2015 Sep 3;16(9):21128-37.; henceforth “Ochiai”). Ochiai specifically evidences the state of the art after the effective filing date of the claimed invention was not routine or conventional and therefore was unpredictable. Ochiai evidences the efficiency of seamless genome editing largely depends on the system and technique used (pg. 21129 3rd para.). Ochiai evidences seamless single-base pair editing and related techniques require highly site-specific programmable nucleases, and exploit homology-directed repair (HDR), one of two major endogenous DSB repair pathways (pg. 21129 3rd para.; Figure 1). Ochiai evidences the use of highly specific programmable nucleases is critical to minimize recutting and insertion of unintended mutations by NHEJ (pg. 21132 1st para.; Figure 1A,B).
Concerning ZFNs, Ochiai evidences single nucleotide editing with ZFNs is unpredictable. Specifically, Ochiai evidences ZFNs are limited in the range of sequences they can target, and, therefore, an appropriate ZFN may not be available for a target base pair (pg. 21132 1st para.). Ochiai evidences preparation of ZFNs with the desired specificity is extremely labor-intensive and as a result, these nucleases are not widely used in academic research (pg. 21132 1st para.).
Concerning TALENs, Ochiai evidences TALENs, in most cases, cannot distinguish a single nucleotide mismatch. Thus, TALENs are not suitable for seamless genome editing by selection-independent methods (pg. 21132 2nd para.).
Ochiai further evidences the identification and isolation of cells with the intended nucleotide changes are a major challenge (p g. 21132 3rd para.). Ochiai evidences selection-dependent methods are labor-intensive, and require two rounds of editing and the intended nucleotide substitution is not always integrated into the genome, and insertion efficiency depends to a significant extent on the distance between the desired mutation and the cut site of the programmable nuclease (pg. 21132 5th para.).
Concerning the Cre-loxP system, Ochiai evidences loxP site is left behind as a footprint and may confound the effects of the intended substitutions (pg. 21133 2nd para.; Figure 1C). Furthermore, the system also has off-target concerns as programmable nucleases (pg. 21133 2nd para.).
Concerning piggyBac-Mediated Excision, Ochiai evidences Excision of the transposon leaves a TTAA fragment behind, a scar that may, as noted, complicate the interpretation of results (Figure 1C; pg. 21133 3rd para.).
Concerning programmable nucleases, Ochiai evidences the need to design these additional programmable nucleases is a drawback, as is the additional risk of off-target effects from such secondary enzymes (pg. 21133 4th para.).
Concerning all editing types, Ochiai evidences that although Genome editing with programmable nucleases enables efficient, seamless substitutions of a single or a small number of nucleotides at predefined sites, technical hurdles remain, and prevent widespread adoption (pg. 21134). Concerning CRISPR, Ochiai postulates single-nucleotide editing with ssODN templates will become highly efficient if programmable nucleases could be engineered to have broad targetable sequences, high specificity, and sensitivity to single-nucleotide mismatches (pg. 21134). In other words, Ochiai evidences that single-nucleotide editing with CRISPR requires additional experimentation and had not yet been achieved as of 2015, which is after the affective filing date of the claimed invention.
In sum, the art of Ochiai evidences that single base pair editing methods require specific design criteria and are generally unpredictable for the reasons stated above due to limitations in target regions, insertion efficiency and off target concerns and Ochiai further evidences that single base pair editing has not yet been achieved as of 2015, which is after the affective filing date of the claimed invention. Therefore, because methods of single base pair editing were not predictable as of 2015, which is after the effective filing date of the claimed invention, Applicant is not enabled for single base pair editing methods encompassed by instant claims.
Results of the claimed method
Instant claims do not recite or require a functional result and do not recite or require a purpose or intended use. Because Applicant has not disclosed an actual reduction to practice, and the state of art evidences the method is unpredictable, Applicant has disclosed no enabled use for the claimed method. Applicant is directed to MPEP 2164 which states that the information contained in the disclosure of an application must be sufficient to inform those skilled in the relevant art how to both make and use the claimed invention (MPEP 2164). Therefore, because the disclosure does not provide an enabled use for the claimed method, it does not comply with the enablement requirement of 35 U.S.C. 112(a).
Unpredictability of the Art and the Quantity of Experimentation
Applicant’s claims do not set forth any active method steps other than the location of the deletion to be made, and simply state making the deletion “using a gene-editing technology.” Gene editing technologies were not predictable as of the effective filing date of the claimed invention, as demonstrated by the arts of Gaj, Carlson, Wu, Ochiai and Heo as discussed above. The obstacles that hinder the use of the claimed method in are not easy tasks to be done or solely routine experimentation. The type of experimentation would require new methodologies. This level of experimentation goes beyond what would be routine optimization know at the time of filing. As such, the amount of experimentation would be undue.
The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112(a) requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to practice the instant broadly claimed invention.
Enablement - Conclusion
In conclusion, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to practice the method of the invention.
Response to Arguments
Applicant’s arguments, filed 2nd, December 2025, have been fully considered and are not found persuasive.
Applicant argues “The Office appears to acknowledge that the specification provides
sufficient direction or guidance with respect to the genetic alteration recited in the amended
claims. See Action, pages 9-10.” (pg. 6).
In response, pg. 9-10 of the previously set forth office action state the amount of direction or guidance presented with respect to a total analyses of the Wands factors. There is no statement or admission that the direction or guidance provided is sufficient. Specifically, the previous action states “Applicant provides limited guidance on using a gene editing technology to make the deletions” (pg. 9) and “the applicant has provided the location of one genetic alteration of a frameshift deletion at chr20:39136559delC specifically in Bos taurus (Table 3 pg. 46 and Table 3 pg. 74), which corresponds to ONLY the embodiment of “deletion of a cytosine (C) at a position corresponding to position 39136559 of chromosome 20 of Bos taurus.”” (pg. 10). This statement specifically refers to the support for the deletion contemplated as part of the total analyses and does not anywhere indicate that this is an enabled embodiment or is sufficient. Later in the previously set forth action, it is explicitly stated that “Applicant does not cite a specific nuclease, a specific target region or specific components or sequences of the nuclease sequence to be used. These elements are required for one of ordinary skill to reasonably be able to perform the claimed method” (pg. 12). It is noted that the state of the art evidences the lack of predictability in the art as discussed previously and as set forth above. The previously set forth rejection was a full lack of enablement rejection and did not indicate an enabled scope. The new grounds of rejection above, necessitated by amendment, is also a full lack of enablement rejection for the reasons set forth above and does not indicate an enabled scope.
Applicant argues “As explained by Professor Snell, the specification provides sufficient guidance to predictably practice the claimed method. Snell Declaration, paragraph 8. As of May 2014, it was routine to design and select reagents for excising one or more nucleotides from a cellular genome using, e.g., TALENs, ZFNs, or CRISPR-Cas9 guide RNAs. Once a target DNA sequence and proposed modification was identified, as is the case in the context of the instant application and claims, standard tools
and published criteria enabled the identification of candidate target sites within the region of
interest, and it was routine to select the components of the gene editing system to achieve
the desired modification. Id., paragraph 6. One of ordinary skill in the art had the requisite
skill and knowledge to select a "specific nuclease, a specific target region or specific
components or sequences of the nuclease sequence to be used." In this regard, the
scientific literature available prior to the filing date of the application described methods for
identifying particular gene editing tools to achieve a desired genomic modification and
performing the desired modification; many of these methods are still in use today. Id.,
paragraphs 9-12. Professor Snell outlines exemplary approaches to achieve the del C
mutation that would have been employed in 2014, methods which were routine in the art at
the relevant time and well documented prior to the filing of the instant application. Id.,
paragraphs 10-11. It was understood by the ordinarily skilled artisan that the published
methods were applicable across species and applicable to livestock, including Bos taurus.
Id., paragraph 7.” (pg. 7).
Applicant argues “Regarding Gaj, Professor Snell states that the paper would not convey to a
researcher in 2014 that gene editing methods were unpredictable. The article characterizes
TALENs/ZFNs/CRISPR as forefront tools and expressly teaches that CRISPR/Cas9 can be
retargeted to virtually any DNA sequence by redesigning the guide. Snell declaration,
paragraph 13. As explained by Professor Snell, any "limitations" of systems described in Gaj
are not features imparting unpredictability in their use, but are requirements that are typical
of any biological system. Id. It is not uncommon for review articles such as Gaj to detail
these types of unique features of different reagents in the course of providing a survey of
different techniques. Id. According to Professor Snell, Gaj conveys that the state of the art
was advanced such that the ability to target genomic regions of interest, in a variety of
contexts, was routine. Contrary to the assertions of the Office, Professor Snell confirms that
Gaj would not convey that TALENs, ZFNs, and CRISPR systems were unpredictable to
someone practicing in the field in May 2014. Id.” (pg. 8).
Applicant argues “Turning to Carlson, the reference includes a typical introduction mentioning
potential obstacles associated with a technology of interest. However, Professor Snell states that the paper would not convey to the ordinarily skilled artisan in 2014 that use of gene editing in livestock was unpredictable. Id., paragraph 14. The results reported in the paper demonstrate efficient gene knockout using engineered nucleases in pigs and cattle cultured cells and embryos. As explained by Professor Snell, one of ordinary skill would not have interpreted any suggestion in Carlson that TALEN editing can result in different indels as imparting unpredictability in the methods. One of ordinary skill would interpret the teachings of Carlson as conveying that targeted disruption is achievable with routine
screening of a few designs, which is typical of any biological system and not "undue." Professor Snell points to Table 1, page 17384, as reporting that the efficiency of nonhomologous end-joining (NHEJ) ranges between 8-77% of clones and, in his opinion, with this "high editing rate," the reference conveys that it would have been straightforward to obtain a cell of interest carrying the desired mutation. Id.” (pg. 8-9).
Applicant argues “Professor Snell also comments on the Yu reference at paragraph 15 of the declaration, explaining that the ordinarily skilled artisan would not interpret the reference as conveying unpredictability in the field. While the authors discussed potential obstacles associated with gene editing, the authors report "high efficiency" gene editing at a target site. Id., paragraph 15. Any disclosure in Yu reporting that some tested ZFNs did not meet the authors' goals does not cast doubt on the general predictability of gene editing in cattle. Id. As explained by Professor Snell, it is common for some aspects of any biological procedure not to perform as intended. Id. The Office's reliance on this type of disclosure in Yu is misplaced and fails to consider the teachings of the reference as a whole as it would be interpreted by the ordinarily skilled artisan. Here, the results of Yu would not convey to those in the field in 2014 that gene editing of a specific target site in cattle is unpredictable. Id. On the contrary, the authors report successful selection of gene editing reagents and successful editing in different bovine cell lines employing a routine level of skill and routine amount of experimentation for the field. Id.” (pg. 10)
Applicant argues “Finally, Professor Snell addresses the Heo reference at paragraph 16 of the
declaration. Heo provides a history of gene editing technology, referencing papers from
2002 and earlier, which is not representative of the state of the art in 2014. Id., paragraph
16. Heo references "highly efficient gene targeting in the bovine genome" and references
CRISPR/Cas9 nuclease mediated homologous recombination targeting in bovine cells as
"an efficient gene editing method." Thus, the reference as a whole conveys that gene editing
is an efficient means of genomic modification.” (pg. 10).
Applicant argues “The Office asserted 'The type of experimentation [to practice the claimed
invention] would require new methodologies." On the contrary, Professor Snell explains that
any "experimentation" necessary was routine and well understood in 2014. The Office's
conclusion does not align with the state of the art, as evidenced by the Rule 132 declaration.
The instant application provides sufficient guidance to perform the full scope of the claimed
method, particularly when considered in light of the teachings of the scientific literature
available in 2014. The Snell declaration provides evidence, from the perspective of the
ordinarily skilled artisan in 2014, establishing that only routine techniques were required to
generate a cell or embryo as claimed with a reasonable expectation of success, which is all
that Section 112 requires” (pg. 10).
In response, the Declaration of Professor Snell is further specifically addressed below. In brief, the evidence provided in the Declaration of Professor Snell is an expert opinion. Applicant is directed to MPEP 716.01(c)(III) which states that although factual evidence is preferable to opinion testimony, such testimony is entitled to consideration and some weight so long as the opinion is not on the ultimate legal conclusion at issue. While an opinion as to a legal conclusion is not entitled to any weight, the underlying basis for the opinion may be persuasive. In re Chilowsky, 306 F.2d 908, 134 USPQ 515 (CCPA 1962) (expert opinion that an application meets the requirements of 35 U.S.C. 112 is not entitled to any weight; however, facts supporting a basis for deciding that the specification complies with 35 U.S.C. 112 are entitled to some weight). In the instant case, the perspective of the ordinarily skilled artisan in 2014, is the expert opinion of Professor Snell, and it is the underlying basis of the opinion which is given weight. The declaration itself does not provide factually objective evidence that “from the perspective of the ordinarily skilled artisan in 2014, establishing that only routine techniques were required to
generate a cell or embryo as claimed with a reasonable expectation of success, which is all
that Section 112 requires” which is discussed further below.
Further in response, for the reasons discussed above, the preponderance of the evidence is that it would require undue experimentation for one or ordinary skill to practice the method of the invention. The state of the art at the time of filing evidences gene editing was not predictable at the time of filing, and further, as discussed above, Applicant’s claim now specifically encompasses single nucleotide deletions editing which was still not predictable at 2015, post-filing, as evidenced by Ochiai above.
Regarding Applicant’s assertation that the methods were routine and well-documented and that the instant application provides sufficient guidance to perform the full scope of the claimed method, particularly when considered in light of the teachings of the scientific literature available in 2014, arguments of counsel cannot take the place of factually supported objective evidence in the record. See In re Schulze, 346 F.2d 500, 602, 145 USPQ 716, 718 (CCPA 1965), In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Thus, Attorney statements alleging that the methods were routine and well-documented are not sufficient to overcome the rejection of record without supporting evidence (see also MPEP 716.01(c) (II)).
Regarding Applicant’s statement that the Office's conclusion does not align with the state of the art, the rejection of record set forth above evidences numerous reasons the state of the art is unpredictable.
Furthermore, as set forth previously and as set forth above, Applicant merely provides the location of a deletion to be made in a prophetic example. Though working examples are not always required, the prophetic example disclosed by Applicant is not sufficient to enable any embodiments of the claims for the reasons set forth above. Applicant does not provide any guidance or other active method steps for any gene editing method and Applicant does not cite a specific nuclease, or specific components or sequences of the nuclease sequence to be used. These elements are required for one of ordinary skill to reasonably be able to perform the claimed method.
Applicant is directed to MPEP 2164.06(b) (I) which cites Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 52 USPQ2d 1129 (Fed. Cir. 1999). In Enzo Biochem the court held that two patents with claims directed to genetic antisense technology (which aims to control gene expression in a particular organism), were invalid because the breadth of enablement was not commensurate in scope with the claims. Both specifications disclosed applying antisense technology in regulating three E. coli genes. Despite the limited disclosures, the specifications asserted that the "[t]he practices of this invention are generally applicable with respect to any organism containing genetic material which is capable of being expressed … such as bacteria, yeast, and other cellular organisms." Thus, the court construed the claims to encompass the application of antisense methodology in a broad range of organisms. Ultimately, the court relied on the fact that (1) the amount of direction presented and the number of working examples provided in the specification were very narrow compared to the wide breadth of the claims at issue, (2) antisense gene technology was highly unpredictable, and (3) the amount of experimentation required to adapt the practice of creating antisense DNA from E. coli to other types of cells was quite high, especially in light of the record, which included notable examples of the inventor’s own failures to control the expression of other genes in E. coli and other types of cells. Thus, the teachings set forth in the specification provided no more than a "plan" or "invitation" for those of skill in the art to experiment using the technology in other types of cells.
In the instant case, analogous to Enzo Biochem, Inc. v. Calgene, the teachings set forth in the specification provided no more than a "plan" or "invitation" for those of skill in the art to experiment using a gene-editing technology and further the specifying relies entirely on the state of the art for all other steps of the method besides the deletion location.
Applicant is additionally directed to MPEP 2164.06 (a) which states that it is common that doubt arises about enablement because information is missing about one or more essential claim elements or relationships between elements which one skilled in the art could not develop without undue experimentation. In the instant case, the instant Application provides no information on essential elements required to enable to claim method including a specific nuclease, or specific components or sequences of the nuclease sequence to be used. Because the gene editing methods are not predictable for the reasons set forth above, these elements are required to enabled the claimed method.
Applicant argues “Regarding the Wu reference, the Office states "Wu is a distinct method which
is cited to evidences inherent characteristics of the lack of predictability of gene editing and more specifically of TALEN editing, and to show that TALEN edited cattle had not been made as of the effective filing date." However, the statements in Wu relied upon by the Office as allegedly suggesting unpredictability is limited to knock-in's, whereas the instant claims require deletion of a cytosine. The reference does not cast doubt on the general predictability of TALEN for gene editing in livestock. Wu states" .. TALEN-mediated site specific transgenesis has been applied successfully to model animals (7, 14-16) and even in large livestock, such as pigs and cattle (17-21)". See page E1530, col. 1.” (pg. 9).
In response, although the Wu reference concerns knock-ins, the lack of predictability is analogous to knock outs, as discussed with the other references of record above. Although Wu states that TALEN-mediated site specific transgenesis has been applied successfully to model animals (7, 14-16) and even in large livestock, such as pigs and cattle, the references still evidences that uses of TALEN to edit cattle is unpredictable because Wu states evidences TALEN induces a double-strand break (DSB) at a precise, defined position in the genome, resulting in unpredictable gene mutations when the DSBs are repaired erroneously by nonhomologous end joining (NHEJ) (pg. E1520 col. 1 1st para.) as set forth above.
Applicant argues “Wu further references the work of Proudfoot et al. relating to TALEN-mediated gene knockouts in sheep and cattle. See, e.g., Wu at page E1537, col. 1, stating "Most recently, Proudfoot et al. (21) reported that they have created myostatin gene knockout sheep and cattle using TALENs." Proudfoot et al. (2015) Transgenic Res 24(1 ): 147-153 (manuscript submitted July 11, 2014, accepted August 26, 2014, and published on line September 10, 2014), is provided herewith for the convenience of the Office. Notably, the Proudfoot reference provides photographs of mature MSTN gene-edited bovine in Figure 2, confirming the ability to make an embryo capable of generating a Bos taurus animal using TALEN gene editing methods in 2014.1 The Proudfoot authors characterize the work reported in the article as exemplifying "the utility and ease with which TALENs can be used to engineer the genome of livestock." Proudfoot, page 152, column 1 (emphasis added)” (pg. 9).
In response, the reference of Proudfoot enables the creation of a materially different gene edited cattle. For the reasons set forth above, TALEN editing of a specific location is still unpredictable and further it is not predictable for the single nucleotide deletion encompassed by instant claims as evidenced by Ochiai, as discussed above. Although the Proudfoot authors characterize the work reported in the article as exemplifying "the utility and ease with which TALENs can be used to engineer the genome of livestock." Proudfoot, page 152, column 1, the state of the art above indicates that gene editing methods are not predictable and further Ochiai evidences that although Genome editing with programmable nucleases enables efficient, seamless substitutions of a single or a small number of nucleotides at predefined sites, technical hurdles remain, and prevent widespread adoption (pg. 21134).
Response to Arguments - Conclusion
The issue with respect to enablement of instant claims is not whether it is possible at all to make the claimed cell, embryo, or animal. The issue is whether one of ordinary skill would have been able to make and use the invention as of the effective filing date of the claimed invention without undue experimentation. The information contained in the disclosure of an application must be sufficient to inform those skilled in the relevant art how to both make and use the claimed invention (see MPEP 2164). In the instant case, the only guidance provided by the specification is the location of the deletion and a statement that it can be made with gene editing of the art. This guidance is presented as a prophetic example. There are no working examples with actual reduction to practice. Applicant’s disclosure of the location of the deletion and a statement that it can be made with gene editing appears to be “no more than a "plan" or "invitation" for those of skill in the art to experiment using the technology” (see MPEP 2164.06 (b)). The state of the art above evidences that gene editing methods at the time of filing were highly unpredictable due to low targeting efficiencies, toxicity, off target effects, limitations in target regions, and technical hurdles specific to single nucleotide editing. It is noted that the references cited in the grounds of rejection above enables specific embodiments of materially distinct methods, as they do arrive at some success in editing animals in those materially distinct methods. However, the fact that ordinarily skilled artisans have made materially different animals each with their own materially distinct methods does not cure the deficit of the instant Application because information is missing about one or more essential claim elements or relationships between elements (the required nucleases and targets specific to each nuclease) (see MPEP 2164.06 (a)) and the preponderance of the evidence based on the totality of the record is that it would require undue experimentation for an ordinarily skilled artisan to arrive at these elements. For the reasons set forth above, because the preponderance of the evidence is that the state of the art evidence that gene editing methods as the time of filing were unpredictable, and because the disclosure of Applicant appears to be “no more than a "plan" or "invitation" for those of skill in the art to experiment using the technology” (see MPEP 2164.06 (b)), the preponderance of the evidence is that one skilled in the art could not develop the required elements to practice the claimed method without undue experimentation and therefore the claims are not enabled.
The Declaration under 37 C.F.R. § 1.132 is addressed further below.
Response to Declaration under 37 C.F.R. § 1.132
The Declaration under 37 CFR 1.132 filed 2nd, December, 2022 is insufficient to overcome the rejection of claims 10-11, 13-15, 28-29 under 35 U.S.C. 112(a) Enablement as set forth in the last Office action and under the new grounds of rejection above for the reasons stated below.
The Declaration recites that “As of May 2014, it was routine to design and select reagents for excising one or more nucleotides from a cellular genome using, e.g., TALENs, ZFNs, or CR!SPR-Cas9 guide RNAs” (para. 6 pg. 2). In sum the declaration, cites publications reporting gene editing methodology available in 2014 (para. 7. pg. 3). The Declaration contests the office’s stance on the art of record and states, in sum, that Gaj (para. 13), Carlson (para. 14), Heo (para. 16) as well as the additional art of Yu (para. 15) and Tan (para. 12) support that the gene editing methods were routine and were not unpredictable.
The declaration cites the following statements from the references as allegedly supporting that the gene editing methods were routine:
“Previous livestock gene editing work from the same group was reported in Tan et aL, PNAS, 110(41 ), ·16526 (October 2013), which reports "precise, high-frequency editing of 15 genes in pig, goat, and cattle genomes," (para. 12).
“Gaj et al., Trends BiotechnoL 2013 May 9;31 (7):397-405, does not cast doubt on the predictability of these tools to a reader in 2014. The paper mentions limitations associated with legacy methods, but the paper would not convey to a researcher in 2014 that the methods were unpredictable. On the contrary, the article characterizes TALENs/ZFNs/CRiSPR as forefront tools and expressly teaches that CRISPR/Cas9 can be retargeted to virtually any DNA sequence by redesigning the guide, which was well within the skill of the ordinary researcher in May 2014. Any "limitations" of systems described in Gaj (e.g., the particular requirements for particular systems, such as the requirement for a PAM site for CR!SPR systems) are not features imparting unpredictability in their use” and “Gaj would not convey that TALENs, ZFNs, and CRISPR systems were unpredictable to someone practicing in the field in May 2014. (para. 13).
“Carlson et al., Proc Natl Acad Sci USA. 2012 Oct 23;109(43): 17382-7, does not convey that use of gene editing in livestock was unpredictable as of May 2014.” “The "take-home message" for an ordinary researcher in the field is that, despite variable individual outcomes of specific TALEN designs, targeted disruption is achievable with routine screening of a few designs.” The authors provide evidence in Table 1, page 17384, that the efficiency of NHEJ ranges between 8--77% of clones. In my opinion, with this high editing rate, it would have been straightforward to obtain a cell of interest carrying the desired mutation and identify mutants by genetic screening for nuclear transfer” (para. 14).
“Any suggestion in Yu et al. (Gel! Res. 2011) that targeting a specific genetic mutation is unpredictable, in my opinion, is a deliberately exaggerated statement for publication gamesmanship to make the authors' subsequent experimental success seem more impactful and achieve a publication. A contrary interpretation of the reference ignores the state of the field at the relevant time. The Yu authors reported that t!1ey tested three pairs of ZFNs in bovine foetus fibroblast cells (Supplementary information, Table S1 ). Design 1 was '19/98 (19.4%) and was the design chosen for the further ZFN edits. "The BLG-set1 cut the targeting site efficiently and was thus selected for the following work," "High-efficiency disruption was achieved when the ZFNs of BLG-set1 were tested in different bovine cell lines" (p1638). In effect, the authors contradicted their initial statement regarding unpredictability through the outcomes of their work showing "high efficiency'' gene editing at a target site. it is worth noting that reports in Yu that some tested ZFNs did not perform satisfactorily with respect to the authors' goals does not cast doubt on the predictability of gene editing in cattle. As in any scientific field or endeavor, some aspects of a procedure may not perform as intended.” (para. 15).
In response, this is not found sufficient to overcome the enablement issues discussed above. It is noted that the cited references do successfully edit cells and livestock. These editing methods are materially distinct methods which each have their own specific method steps, nucleases or other gene editing methods, and targets. As a whole, these methods do evidences that gene editing generally can be performed. The issue at hand is not whether gene editing could be performed, but whether, with the total of the evidence of the record, it would require undue experimentation for a person of ordinary skill in the art to perform the method of Applicant’s claims without undue experimentation.
It is noted that the Declaration takes the position that the gene editing methods were routine and were not unpredictable based on the cited art. This aspect of the declaration is a conclusion based on the art, and it not itself objective evidence. Applicant is directed to MPEP 716.01 (c) (III) which states that while an opinion as to a legal conclusion is not entitled to any weight, the underlying basis for the opinion may be persuasive. In re Chilowsky, 306 F.2d 908, 134 USPQ 515 (CCPA 1962) (expert opinion that an application meets the requirements of 35 U.S.C. 112 is not entitled to any weight; however, facts supporting a basis for deciding that the specification complies with 35 U.S.C. 112 are entitled to some weight). In the instant case, the assertations themselves that the gene editing methods were routine and were not unpredictable based on the cited art is not entitled to any weight, while the cited facts (the objective findings of the cited art) are entitled to some weight. MPEP 716.01 (c) (III) further states in assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established, the strength of any opposing evidence, the interest of the expert in the outcome of the case, and the presence or absence of factual support for the expert’s opinion and although an affidavit or declaration which states only conclusions may have some probative value, such an affidavit or declaration may have little weight when considered in light of all the evidence of record in the application. In re Brandstadter, 484 F.2d 1395, 179 USPQ 286 (CCPA 1973)
In the instant case, as set forth previously and as set forth above, the objective facts cited which are the objective findings of the cited art are not sufficient to overcome the rejection under 35. U.S.C. 112(a) for enablement. Specifically, for the reasons set forth previously and set forth above, in light of all the evidence of the record, it appears to the examiner that the state of the art above evidences that gene editing methods at the time of filing were highly unpredictable due to low targeting efficiencies, toxicity, off target effects, limitations in target regions, and technical hurdles specific to single nucleotide editing for the reasons set forth in the grounds of rejection above.
Further, the fact that ordinary skilled artisans have made materially different animals each with their own materially distinct methods does not cure the deficit of the instant Application because information is missing about one or more essential claim elements or relationships between elements (the required nucleases and targets specific to each nuclease) (see MPEP 2164.06 (a)). The fact that ordinarily skilled artisans have made materially different animals each with their own materially distinct methods does not lead one of ordinary skill to be able to obtain the missing information of the instant application without undue experimentation. Because the disclosure of Applicant appears to be “no more than a "plan" or "invitation" for those of skill in the art to experiment using the technology” (see MPEP 2164.06 (b)), the preponderance of the evidence is that one skilled in the art could not develop the required elements to practice the claimed method without undue experimentation and therefore the claims are not enabled.
The Declaration specifically cites Sonstegard et al. (US-2017/0079251-A1; see IDS filed 2nd, December, 2025; henceforth “Sonstegard”) and alleges the publication describes work performed prior to September 2015 pg. 5 para. 12).
In response, as set forth above it is the cited facts (the objective findings of the cited art) which are entitled to weight and these are not sufficient for the Sonstegard art for the following reasons.
The instant Application is a divisional of U.S. Patent No. 10779518 which claims priority to PCT/NZ2014/000224 filed 24th, October, 2024 which also claims the benefit for foreign applications NEW ZEALAND 617040 filed 10/25/2013, NEW ZEALAND 625150 filed 05/20/2014, NEW ZEALAND 627209 filed 07/08/2014, and NEW ZEALAND 630540 09/12/2014, which is earlier than September, 2015. As such, it is unclear whether the work was performed prior to the earliest effective filing date of the claimed invention. US-2017/0079251-A1 corresponds to Application 15/270,901. It is noted that Application 15/270,901 has not been patented and it now abandoned. It is noted that Application 15/270,901, corresponding to US-2017/0079251-A1 is not under consideration here. However, the disclosure of US-2017/0079251-A1, provides Examples 4-6 which are prophetic examples for making the cattle. Other examples in US-2017/0079251-A1 are drawn to editing cells only. Thus, US-2017/0079251-A1 does not cure the deficiency of the instant Application in making Bos taurus cells, embryos, or animals with the claimed deletion and further as it is noted above, instant claims encompass single nucleotide edits which were not predictable as of the effective filing date of the claimed invention.
New Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10-11, 13-15 and 28-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites the active method step of “deleting a single nucleotide consisting of a cytosine (C) at position 39136559 of chromosome 20 of Bos taurus” which indicates the deletion is performed on Bos taurus animals. However, the preamble of the claim states “a method of producing a Bos taurus cell or embryo” and the thereby clause states “thereby producing a cell or embryo.” Because the term “Bos taurus” of the claim can refer to the full species or an individual animal, while the claims require a result of producing a cell or embryo, the scope of the claim is unclear. Specifically, while performing the deletion in a Bos taurus animal can result in a cell of that animal having the deletion, it is unclear how the method step of performing the deletion in a Bos taurus animal can result in an embryo.
By nature of their ultimate dependency on claim 10, claims 11, 13-15 and 28-29 are also rejected because they do not clarify the issue.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632