DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 01 October 2025, have been entered. Claims 1-3, 8, 15, 21, 24-27, 29, 52-54, 60, 63, 73, 76-77, and 81 are currently pending. Claims 1 and 76 are independent claims. Applicant’s election of the following species:
Preselected heritable trains: c. sterile-daughter heritable trait;
Gene delivery methods: a. in vitro fertilization;
in a reply filed 01 October 2025 is acknowledged. While Applicant has not indicated whether these elections of species have been made with or without traverse, Applicant has not provided any arguments traversing the election of species requirement(s). Therefore, the election of species sterile-daughter heritable trait and in vitro fertilization is considered to have been made without traverse.
Claims 21, 24-27, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2020/61504, filed 20 November 2020, which claims priority to U.S. Provisional Application No. 62/938,532, filed 21 November 2019.
Thus, the earliest possible priority for the instant application is 21 November 2019.
Information Disclosure Statement
The information disclosure statement filed 20 May 2022 has been considered by the Examiner.
Specification
The disclosure is objected to because of the following informalities: the specification recites, “Fib. 1B” on page 10 line 25, which appears to be a typographical misspelling of “Fig. 1B”.
Appropriate correction is required.
Claim Objections
Claim 73 is objected to because of the following informalities: claim 73 recites “the method of claim 2, further comprising, capturing” wherein the presence of comma after “comprising” appears to be a typographical error. Appropriate correction is required.
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 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 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.
Independent claim 1 recites the limitation "the introduction" in line 6. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites “for introduction” in line 3 and “introducing” in line 5. As such, the metes and bounds of the claim cannot be determined.
Claim 2 recites, “a captive female” in line 3 and “the captive female” in line 4, which is indefinite because the scope of the term “captive” it is unclear in that it is unclear in what respect the female is captive. For example, it is unclear whether “captive” is meant to denote any female subject which is at least temporarily under the control of the individual performing the delivering, impregnating, and releasing steps, whether “captive” indicates that the female does not have freedoms normally had by members of her species (such as freedom of movement), and/or whether “captive” is meant to denote that the female is not consenting to the procedures being carried out. Note that the broadest reasonable interpretation of independent claim 1, upon which claim 2 depends, encompasses a human species. As such, it is unclear whether claim 2 is meant to encompass delivering, impregnating, and releasing captive female humans gestating offspring with the elected sterile-daughter trait. As such, the metes and bounds of the claim cannot be determined.
Claim 3 recites, “the means of the delivery in (a)” in line 1. There is insufficient antecedent basis for “the means” in the claim. Additionally, it is unclear what step is being referred to in that claim 2, upon which claim 3 depends, has a step of (i) delivering, but no step of (a) delivery step. Further, to the extent that “the delivery in (a)” is meant to refer to the step of “(i) delivering”, it is further unclear how steps (i) and (ii) are distinct method steps if the step of (i) delivering is impregnating the captive female. For example, it is unclear whether the captive female is meant to be impregnated twice. As such, the metes and bounds of the claim cannot be determined.
Claim 53 recites “engineering a Y chromosome that disrupts” in line 2, which is indefinite because it is unclear whether the disruption ability of the Y chromosome is present on the Y chromosome prior to the engineering or whether the disruption ability is the product of the engineering. As such, the metes and bounds of the claim cannot be determined.
Claim 54 has multiple issues of indefiniteness.
Claim 54 recites “engineering a Y chromosome that produces” in line 2, which is indefinite because it is unclear whether the producing ability of the Y chromosome is present on the Y chromosome prior to the engineering or whether the producing ability is the product of the engineering. It is further unclear in what way a Y chromosome “produces” a nuclease, in that the Y chromosome can comprises a nucleic acid sequence encoding a nuclease and the necessary sequences for expression of the nuclease by intracellular factors, but the Y chromosome itself cannot directly produce a nuclease.
Claim 54 additionally recites, “and when present in a zygote”, which is indefinite because it is unclear whether the limitation is referring to the presence of the Y chromosome or the presence of the nuclease.
As such, the metes and bounds of the claim cannot be determined.
Claim 73 recites, “wherein the capturing is aided in part by a determined spatial distribution of engineered organisms introduced by birth into the target population”, which is unclear in that it is unclear whether “determined” requires direct observations of the actual spatial distribution or whether “determined” allows for predictive modeling to develop an expected spatial distribution. Additionally, it is unclear whether “spatial distribution of engineered organisms introduced by birth” is meant to indicate the spatial distribution of the engineered organisms following birth into and subsequent spread within the target population or whether the spatial distribution of the engineered organisms is meant to indicate the spatial distribution at the time of the introduction. As such, the metes and bounds of the claim cannot be determined.
Claim 76 recites, “one or a plurality of captive female organisms” in line 3, “the captive female organisms” in lines 6, 8, and 10, “the impregnated captive female organism” in lines 8-9 and 13, and “the identified impregnated captive female organisms” in line 11, which is indefinite because the scope of the term “captive” it is unclear in that it is unclear in what respect the female is captive. For example, it is unclear whether “captive” is meant to denote any female subject which is at least temporarily under the control of the individual performing the delivering, impregnating, and releasing steps, whether “captive” indicates that the female does not have freedoms normally had by members of her species (such as freedom of movement), and/or whether “captive” is meant to denote that the female is not consenting to the procedures being carried out. As such, the metes and bounds of the claim cannot be determined.
Claims 8, 15, 52, 60, 63, 77, and 81 are included in this rejection due to their dependence on claims 1, 2, and/or 76.
Claim Interpretation
Claim 1 recites “introducing by birth into the target population” in line 5. Note that the specification provides a limiting definition for the phrase “introduction by birth”: “The term ‘introduction by birth’ as used herein, means introduction of one or more preselected heritable traits into a target population using a method of the invention comprising release of an impregnated female host into the target population and the subsequent birth of offspring of the pregnancy when the released female is in the target population.” [page 29 lines 21-25]. Therefore, the step (b) of “introducing by birth into the target population” recited in independent claim 1 has been interpreted in light of Applicant’s provided definition to require the release of an impregnated female host into the target population, wherein the engineered organism being introduced “by birth” refers to an embryo/fetus being gestated by the impregnated female host.
Note further that the specification further teaches “the term ‘target population’ is the population of organisms into which an impregnated female … is released. Non- limiting examples of target populations include a wild population of the organism, an agricultural population of the organism, a human-managed population of the organism, a population of the organisms in a preserve, a population of the organisms in captivity; a zoo population of the organisms. In some embodiments of the invention, a target population is an endangered population of organisms. It will be understood that in some embodiments of the in invention a target population is the population from which the female organism was captured and in some embodiments of the invention the target population is a population of the same species of organism as the captured female, but it is a different population than the one from which the female organism was captured.” [page 16 lines 16-26]. The specification additionally teaches, “It will be understood that in some embodiments of the invention a target population is the population from which the impregnated female organism was obtained prior to the impregnation, and in some embodiments of the invention the target population is a population of the same species of organism as the impregnated female, but is a different population than one from which the female organism was obtained. ” [page 26 lines 10-24]. Accordingly, by teaching that a target population can be a captive population, the term “release” is not limited to an introduction into a target population wherein the impregnated female is no longer captive.
Therefore, “introduction by birth” encompasses wherein an impregnated female is released into a population of organisms in captivity following an impregnation procedure (e.g., the elected IVF procedure), and subsequently gives birth to the engineered organism; including, for example, wherein the captive population is a laboratory population from which the impregnated female was removed prior to undergoing the impregnation procedure.
This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: “wherein a means of introducing the preselected heritable trait by birth” in claim 2 and “wherein the means of the delivery in (a)” in claim 3.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
Further, the recitation in claim 2 line 1 of “a means of introducing” has been interpreted as presenting an exemplary option for the method step of introducing recited in claim 1, which therefore is not a required limitation of the claimed invention.
Claim 15 recites the term “optionally” in line 2, which has been interpreted to indicate that the limitations following the term “optionally” are not required limitations of the claim.
Claim Rejections - 35 USC § 112(a)
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 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
a method of changing or altering a genetic characteristic of a target population of organisms of a non-human species, comprising:
preselecting a heritable trait for introduction into the target population of organisms;
obtaining one or more captive female organisms of the species;
introducing a genetic element comprising a genomic nucleic acid sequence which effects the preselected heritable trait from one or more male organisms of the species into one or more captive female organisms to impregnate the one or more captive females; and
(b) releasing one or more of the impregnated captive females into a target population, thereby introducing by birth into the target population an engineered organism of the species comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population;
wherein the species is selected from the group consisting of a mouse species and a rat species;
wherein the preselected heritable trait is selected from the group consisting of coat color, daughterless-male, and sterile-daughter; and
wherein the genetic characteristic of the target population comprises the genomic nucleic acid sequence which effects the preselected heritable trait;
does not reasonably provide enablement for:
a method of changing a genetic characteristic of a target population of organisms of any species, comprising (a) preselecting any heritable trait for introduction into a target population of any organisms; and (b) introducing by birth into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes any genetic characteristic of the target population.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The rejection comprises three (3) separate issues: 1) the absence of an enabling disclosure for changing a genetic characteristic of a target population of organisms of any species other than a species or mouse or a species of rat; 2) the absence of an enabling disclosure for introducing into a target population of organisms any heritable trait other than a coat color variant, a daughterless male trait, or a sterile-female trait; and 3) the absence of an enabling disclosure for changing any genetic characteristic of the target population other than a genetic characteristic which is a genomic nucleic acid sequence which effects the preselected heritable trait.
These issues were identified by the Office after analysis of the disclosure provided by the specification. The Office has analyzed the specification in direct accordance to the factors outlined in In re Wands, namely 1) the nature of the invention, 2) the state of the prior art, 3) the predictability of the art, 4) the amount of direction or guidance present, and 5) the presence or absence of working examples, and presented detailed scientific reasons supported by publications from the prior art for the finding of a lack of enablement for the scope of the instant methods. The Wands analysis and supporting specific evidence are presented below for each of the identified issues.
As a first issue (1), the specification does not provide an enabling disclosure for changing a genetic characteristic of a target population of organisms of any species other than a species or mouse or a species of rat. The broadest independent claim, claim 1, recites a method of changing a genetic characteristic of a target population of organisms of a species, comprising preselecting a heritable trait for introduction into a target population of organisms; and introducing by birth into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population. Claims 2-3, 8, 15, 52-54, 60, 63, and 73 depend on independent claim 1. Independent claim 76 recites a method of altering a genetic characteristic of a target population of organism of a species, comprising a) obtaining one or a plurality of captive female organisms of a species, wherein the species is a non-human species; b) introducing a genetic element from one or more male organisms of the species into the one or the plurality of the captive female organisms, wherein each of the one or more male organisms exhibits one or more preselected heritable traits; wherein the introducing results in impregnation of at least one of the captive female organisms, and a descendant of the impregnated captive female organism exhibits one or more of the preselected heritable traits; c) identifying one or more of the captive female organisms impregnated in (b); and d) releasing one or more of the identified impregnated captive female organisms into a target population of organisms of the species, wherein the presence of one or more descendants of the impregnated captive female organisms alters a genetic characteristic of the target population. Claims 77 and 81 depend on claim 76.
The specification discloses that in some aspects of the invention, a cell or organism is a vertebrate or an invertebrate cell or organism, a eukaryotic or prokaryotic cell or organism, or any of a list of sexually reproducing organisms including insects, fish, reptiles, amphibians, mammals, rodents, birds, cats, dogs, pigs, pigeons, starlings, fish, carp, trout, ferrets, weasels, stoats, possums, mongooses, mice, squirrels, rats, chipmunks, moles, and voles [page 44 line 28- page 45 line 4]. The examples provided in the specification only provide prophetic examples of studies to be done according to the invention. Examples 1-4 only generally disclose studies to be done with mice or rats. Example 5 provides a more detailed explanation of the genetic alterations to be achieved in mice with a daughterless male phenotype by disrupting the Xist gene on a murine X-chromosome, but does not provide any data for any methods according to the claimed invention and does not provide any details for producing such a trait in any other species. The Figures of the Drawings provide sequence alignments for the Xist gene for M. musculus (mouse), R. norvegicus (rat), F. catus (cat), and human [Figure 1A], specific target sequences within the Xist gene [Figure 1B], and schematics for the daughterless mouse gene drive system which utilizes a modified Y-chromosome expressing a Cas9 nuclease and sgRNAs to target and disrupt the Xist gene to cause heterozygote lethality in females [Figure 2A-B]. As such, the specification and drawings teach that the specific genetic changes to be introduced are species-specific. The specification and drawings provide no data for any changing of any genetic characteristic of any target population for any species.
The art at the time of filing teaches that gene drive elements based on CRISPR/Cas9 nuclease could be used to spread many types of genetic alterations through sexually reproducing species, such as yeast, fruit flies, and mosquitoes [Noble et al. 2016, BioRx, bioRxiv 057307, 1-32, page 3 ¶ 1]. Noble also teaches that each gene drive targets wild-type genomic sequences of the organism [Figure 1], which therefore necessitates design of the drive for each target species. Noble further teaches the design of a gene drive system conferring a sterile-daughter trait specifically in mice [page 12 ¶ 2, Figure S9, S10].
Rode teaches a variety of application for gene drive systems, including eradication, suppression, and rescue drives, which rely on a variety of different genetic changes to evoke the desired effects, such that each desired genetic change is designed specifically for each target species depending on the program goals [Rode et al. 2019, Conservation Genetics, 20, 671-690, published online 1 April 2019, IDS, column 2 ¶ 1- column 4 ¶ 1, Figure 2, Box 1]. Rode also teaches considerations such as gene drive timing of expression [column 7 ¶ 1- column 8 ¶ 1], gene drive genetic parameters [column 9 ¶ 1- column 11 ¶ 1], mating systems [column 11 ¶ 2- column 12 ¶ 1], generation time [column 12 ¶ 2], population structure in space and time [column 12 ¶ 3- column 13 ¶ 2], and density-dependence, age, and social structure [column 13 ¶ 3]. Rode further provides potential examples of applications in conservation, wherein each application has multiple diverse variables to consider in designing and constructing gene drives to alter a heritable trait in the population [column 14 ¶ 1- column 18 ¶ 1, Table 2].
Neither the specification nor the art at the time of filing teaches that any gene or gene allele (e.g., any gene drive) can be introduced into any species to effect a heritable trait which changes a genetic characteristic of a target population. Thus, in view of the need to specifically tailor the genetic constructs for altering a genetic characteristic (e.g., a gene drive construct) to each specific species, the art recognized complexity of designing and constructing such gene drive constructs, the lack of specificity in the specification for designing a gene drive for any species other than mouse, the lack of teachings in the examples of the specification for gene drive implementation in any species other than mouse or rat, and the breadth of the claims, the skilled artisan would have considered changing a genetic characteristic of a target population of organisms of any species other than a species or mouse or a species of rat using the instantly claimed method as highly unpredictable. As such it would have required undue experimentation to practice the scope of applicant’s invention as claimed.
As a second issue (2), the specification does not provide an enabling disclosure for introducing into a target population of organisms any heritable trait other than a coat color variant, a daughterless male trait, or a sterile-female trait. The broadest independent claim, claim 1, recites a method of changing a genetic characteristic of a target population of organisms of a species, comprising preselecting a heritable trait for introduction into a target population of organisms; and introducing by birth into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population. Claims 2-3, 8, 15, 52-54, 60, 63, and 73 depend on independent claim 1. Independent claim 76 recites a method of altering a genetic characteristic of a target population of organism of a species, comprising a) obtaining one or a plurality of captive female organisms of a species, wherein the species is a non-human species; b) introducing a genetic element from one or more male organisms of the species into the one or the plurality of the captive female organisms, wherein each of the one or more male organisms exhibits one or more preselected heritable traits; wherein the introducing results in impregnation of at least one of the captive female organisms, and a descendant of the impregnated captive female organism exhibits one or more of the preselected heritable traits; c) identifying one or more of the captive female organisms impregnated in (b); and d) releasing one or more of the identified impregnated captive female organisms into a target population of organisms of the species, wherein the presence of one or more descendants of the impregnated captive female organisms alters a genetic characteristic of the target population. Claims 77 and 81 depend on claim 76.
The specification generically discloses phenotypic or genotypic traits throughout, with a few examples including coat color, sterile-daughter, daughterless-male, fatherless-male, and antibody expression for disease resistance [page 2, 6, 8, 12, 19]. However, the specification only discloses release studies with or without gene/ gene drive designs for three specific traits for alteration in a target population according to the presently claimed invention: coat color [Example 2], daughterless-male [Example 4-5], and sterile-daughter [page 4] traits. The drawings present sequence information for the Xist gene for four species [Figure 1A], along with a gene drive design for disrupting the Xist gene in mouse to effect a daughterless-male phenotype [Figure 2]. The only specific gene/ gene drives designs presented in the disclosure are for the daughterless-male trait [Examples 4-5, Figures 1-2].
The art at the time of filing teaches that gene drive elements based on CRISPR/Cas9 nuclease could be used to spread many types of genetic alterations through sexually reproducing species, such as yeast, fruit flies, and mosquitoes [Noble page 3 ¶ 1]. Noble also teaches that each gene drive targets wild-type genomic sequences of the organism [Figure 1], which therefore necessitates design of the drive for each target locus/ trait. Noble further teaches the design of a gene drive system conferring a sterile-daughter trait specifically in mice which is designed to target and disrupt murine female fertility genes [page 12 ¶ 2, Figure S9, S10].
Rode teaches a variety of application for gene drive systems, including eradication, suppression, and rescue drives, which rely on a variety of different genetic changes to evoke the desired effects, such that each desired genetic change is designed specifically for each target species depending on the program goals [column 2 ¶ 1- column 4 ¶ 1, Figure 2, Box 1]. Rode also teaches considerations such as gene drive timing of expression [column 7 ¶ 1- column 8 ¶ 1], gene drive genetic parameters [column 9 ¶ 1- column 11 ¶ 1], mating systems [column 11 ¶ 2- column 12 ¶ 1], generation time [column 12 ¶ 2], population structure in space and time [column 12 ¶ 3- column 13 ¶ 2], and density-dependence, age, and social structure [column 13 ¶ 3]. Rode further provides potential examples of applications in conservation, wherein each application has multiple diverse variables to consider in designing and constructing gene drives to alter a different heritable trait associated with different genetic loci in the population [column 14 ¶ 1- column 18 ¶ 1, Table 2].
Neither the specification nor the art at the time of filing teaches that any gene or gene allele (e.g., any gene drive) can be introduced or targeted into any species to effect any heritable trait which changes any genetic characteristic of a target population. Thus, in view of the need to specifically tailor the genetic constructs for altering a genetic characteristic (e.g., a gene drive construct) to each specific trait of each species, the art recognized complexity of designing and constructing such gene drive constructs, the lack of specificity in the specification for designing a method of changing a genetic characteristic in a target population for any traits other than coat color, daughterless-male, or sterile-daughter traits, the lack of teachings in the examples of the specification for gene drive implementation for any traits other than coat color or daughterless-male, and the breadth of the claims, the skilled artisan would have considered changing any genetic characteristic of a target population of organisms of any species other than a trait of coat color, daughterless-male, or sterile-daughter using the instantly claimed method as highly unpredictable. As such it would have required undue experimentation to practice the scope of applicant’s invention as claimed.
As a third issue (3), the specification does not provide an enabling disclosure for changing any genetic characteristic of the target population other than a genetic characteristic which is a genomic nucleic acid sequence which effects the preselected heritable trait. The broadest independent claim, claim 1, recites a method of changing a genetic characteristic of a target population of organisms of a species, comprising preselecting a heritable trait for introduction into a target population of organisms; and introducing by birth into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population. Claims 2-3, 8, 15, 52-54, 60, 63, and 73 depend on independent claim 1. Independent claim 76 recites a method of altering a genetic characteristic of a target population of organism of a species, comprising a) obtaining one or a plurality of captive female organisms of a species, wherein the species is a non-human species; b) introducing a genetic element from one or more male organisms of the species into the one or the plurality of the captive female organisms, wherein each of the one or more male organisms exhibits one or more preselected heritable traits; wherein the introducing results in impregnation of at least one of the captive female organisms, and a descendant of the impregnated captive female organism exhibits one or more of the preselected heritable traits; c) identifying one or more of the captive female organisms impregnated in (b); and d) releasing one or more of the identified impregnated captive female organisms into a target population of organisms of the species, wherein the presence of one or more descendants of the impregnated captive female organisms alters a genetic characteristic of the target population. Claims 77 and 81 depend on claim 76.
The specification generically discloses phenotypic or genotypic traits throughout, with a few examples including coat color, sterile-daughter, daughterless-male, fatherless-male, and antibody expression for disease resistance [page 2, 6, 8, 12, 19]. However, the specification only teaches the relationship between a specific preselected heritable trait with a specific genetic characteristic, such as a gene drive effecting a disruption of the Xist gene with a daughterless-male trait [page 2-3, 8-9, 20, 36, Example 5, Figure 1-2], a gene drive effecting a disruption of a female fertility gene with a sterile-daughter trait [page 4-5], or a coat color variant allele with a coat color trait [page 2, 7, 19].
The art at the time of filing teaches that heritable traits arise from encoded genetic elements, such as sterile-daughter traits resulting from a gene drive system disrupting a female fertility gene [Noble Figure S10].
Neither the specification nor the art at the time of filing teaches that a heritable trait can arise from any genetic characteristic of the target population other than a genetic characteristic which is a genomic nucleic acid sequence which effects the preselected heritable trait itself. Thus, in view of the genotype-phenotype relationships for heritable traits, such that a genomic nucleic acid sequence encodes for mRNA and/or proteins which determine the heritable trait, the lack of teachings in the specification or in the art for introduction of heritable traits which effect changes in genetic characteristics of a population wherein the genetic characteristic is unrelated to the heritable trait, and the breadth of the claims, the skilled artisan would have considered changing any genetic characteristic of a target population of organisms of any species other than a genetic characteristic associated with/ effecting the preselected heritable trait using the instantly claimed method as highly unpredictable. As such it would have required undue experimentation to practice the scope of applicant’s invention as claimed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 8, 15, 52, and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Noble et al. [2016, BioRx, bioRxiv 057307, 1-32].
Regarding claim 1, Noble teaches a method of changing a genetic characteristic of a target population of organisms of a species [page 2 ¶ 2, page 4 ¶ 1], comprising (a) preselecting a heritable trait (e.g., a sterile-daughter heritable trait) for introduction into a target population of organisms [page 12 ¶ 2, Figure S10]; and (b) introducing into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population [abstract, page 2 ¶ 1-2, page 11 ¶ 2-4, page 12 ¶ 4, Figure S10].
Noble does not explicitly teach wherein the introducing is introducing by birth. However, Noble teaches modification of germline cells to introduce the preselected heritable trait and to produce gametes comprising the preselected heritable trait [Figure S3], which necessarily requires the birth of an engineered organism arising from the modified gametes to change a genetic characteristic within a target population/ alter a local population [title, abstract, page 7 ¶ 2]. Therefore, Noble implicitly teaches the birth of an engineered organism comprising the preselected heritable trait. Such a birth necessarily introduces by birth the engineered organism comprising the preselected heritable trait into whatever population the impregnated female is part of at the time of the birth.
Noble further teaches the development of the daisy drive systems in the laboratory [page 12 ¶ 5], wherein such development necessarily includes the genetic engineering of the mice. Noble specifically teaches the introduction of engineered organisms comprising the preselected heritable trait (e.g., the sterile-daughter trait) into wild target populations [abstract, page 11 ¶ 2-4, page 12 ¶ 4]. Such an introduction can occur either a) by introducing the impregnated female gestating the engineered organism into the wild population prior to birth of the engineered organism or b) by introducing the engineered organism, or its descendants, into the wild population following birth of the engineered organism. For either scenario, the impregnated female is introduced at least into the captive laboratory population following the impregnation procedure. As such, if the birth occurs in the laboratory setting, then the introduction by birth has modified a genetic characteristic of the captive laboratory population. If the impregnated female herself is released into the wild population, then the introduction by birth has modified a genetic characteristic of the wild population.
Each of scenarios a) and b) are encompassed by the scope of claim 1 as written. As described above under Claim Interpretation, “introducing by birth” encompasses wherein an impregnated female is released into a population of organisms in captivity following an impregnation procedure (e.g., the procedure which introduces the engineered germline cells or gametes into the female), and subsequently gives birth to the engineered organism; including, for example, wherein the captive population is a laboratory population from which the impregnated female was removed prior to undergoing the impregnation procedure.
Therefore, Noble implicitly teaches the introducing by birth into a target population an engineered organism comprising the preselected heritable trait, wherein the target population is either a captive population within a laboratory setting or a wild population, and wherein the introduction changes a genetic characteristic of the target population.
Regarding claim 2, Noble teaches i) delivering into a reproductive cell (e.g., a germline cell) of a captive individual of the organism a gene or gene allele that when expressed in a descendant of the captive female organism results in an engineered organism that exhibits the preselected heritable trait [Figure S3].
As discussed above for claim 1, the teachings of Noble a) to produce gametes comprising the preselected heritable trait [Figure S3] and b) of the trait spreading in a population to change a genetic characteristic within a target population/ alter a local population [title, abstract, page 7 ¶ 2] together necessarily require the birth of an engineered organism arising from the modified gametes, which also further necessarily requires impregnating a captive female of the organism to facilitate the development of the engineered gamete into an engineered adult organism capable of passing on its genes.
Noble does not teach whether the genetically engineered germline cells giving rise to genetically engineered gametes are male or female. However, editing either male or female germline cells will satisfy the claims as written. The editing of female germline cells represents a direct delivery of the gene or gene allele into a reproductive cell of a captive female. Alternatively, the editing of a male germline cell to produce genetically engineered sperm, which are then used to impregnate a captive female represents an alternative method for delivering the gene into a reproductive cell (e.g., oocyte) of a captive female in that the sperm will deliver its engineered genome into the oocyte upon fertilization.
As also discussed above for claim 1, releasing the impregnated captive female of the organism into the target population of organisms encompasses either introducing the impregnated captive female into a captive (e.g., laboratory) population or into a wild population. Noble teaches releasing engineered individuals comprising the preselected heritable trait into a wild population following a genetic engineering of the germ cells/ gametes, and thus necessarily implicitly teaches releasing/introducing the impregnated captive female into at least a target captive laboratory population and/or a target wild population of organisms.
Regarding claim 8, Noble teaches wherein the engineered organism is a male engineered organism by 1) teaching that the heritable trait is a male-linked sterile-daughter trait, wherein a male produces sons like himself and daughters that are sterile, such that only males can pass the trait on to descendants [Figure S10], and 2) that engineered males should remain in the population for an extended period once released [Figure S10].
Regarding claim 15, Noble teaches wherein the organism is a mammal (e.g., mouse) [Figure S1, S9, S10].
Regarding claim 52, Noble teaches wherein the preselected heritable trait is a sterile-daughter heritable trait [Figure S10].
Regarding claim 54, Noble teaches wherein the sterile-daughter heritable trait is generated by engineering a Y chromosome that produces a nuclease (e.g., Cas9 nuclease) carried in sperm of the engineered male organism and when present in a zygote, the nuclease cuts one or more female-specific fertility genes [page 3 ¶ 1, page 11 ¶ 1, page 12 ¶ 2, Figures S1, S9, S10].
Accordingly, by teaching all of the limitations of claims 1-2, 8, 15, 52, and 54 as written, Noble anticipates the instant invention as claimed.
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 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) 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 are rejected under 35 U.S.C. 103 as being unpatentable over Noble et al. [2016, BioRx, bioRxiv 057307, 1-32]; in view of Taft [2017, Cold Spring Harbor Protocols, 886-892]; Brigham and Women’s Hospital [2019, In Vitro Fertilization (IVF), retrieved on 21 January 2026 from the Internet: <https://www.brighamandwomens.org/obgyn/infertility-reproductive-surgery/infertility-services/in-vitro-fertilization>, archived on 17 September 2019]; Esvelt [US20160333376A1, published 17 November 2016]; and Turner et al. [2018, BMC Proceedings, 12(Suppl 8): 13, 53-64].
Regarding claim 1, Noble teaches a method of changing a genetic characteristic of a target population of organisms of a species [page 2 ¶ 2, page 4 ¶ 1], comprising (a) preselecting a heritable trait (e.g., a sterile-daughter heritable trait) for introduction into a target population of organisms [page 12 ¶ 2, Figure S10]; and (b) introducing into the target population an engineered organism comprising the preselected heritable trait, wherein the introduction changes a genetic characteristic of the target population [abstract, page 2 ¶ 1-2, page 11 ¶ 2-4, page 12 ¶ 4, Figure S10].
Noble does not explicitly teach wherein the introducing is introducing by birth. However, Noble teaches modification of germline cells to introduce the preselected heritable trait and to produce gametes comprising the preselected heritable trait [Figure S3], which necessarily requires the birth of an engineered organism arising from the modified gametes to change a genetic characteristic within a target population/ alter a local population [title, abstract, page 7 ¶ 2]. Therefore, Noble implicitly teaches the birth of an engineered organism comprising the preselected heritable trait. Such a birth necessarily introduces by birth the engineered organism comprising the preselected heritable trait into whatever population the impregnated female is part of at the time of the birth.
Noble further teaches the development of the daisy drive systems in the laboratory [page 12 ¶ 5], wherein such development necessarily includes the genetic engineering of the mice. Noble specifically teaches the introduction of engineered organisms comprising the preselected heritable trait (e.g., the sterile-daughter trait) into wild target populations [abstract, page 11 ¶ 2-4, page 12 ¶ 4]. Such an introduction can occur either a) by introducing the impregnated female gestating the engineered organism into the wild population prior to birth of the engineered organism or b) by introducing the engineered organism, or its descendants, into the wild population following birth of the engineered organism. For either scenario, the impregnated female is introduced at least into the captive laboratory population following the impregnation procedure. As such, if the birth occurs in the laboratory setting, then the introduction by birth has modified a genetic characteristic of the captive laboratory population. If the impregnated female herself is released into the wild population, then the introduction by birth has modified a genetic characteristic of the wild population.
Each of scenarios a) and b) are encompassed by the scope of claim 1 as written. As described above under Claim Interpretation, “introducing by birth” encompasses wherein an impregnated female is released into a population of organisms in captivity following an impregnation procedure (e.g., the procedure which introduces the engineered germline cells or gametes into the female), and subsequently gives birth to the engineered organism; including, for example, wherein the captive population is a laboratory population from which the impregnated female was removed prior to undergoing the impregnation procedure.
Therefore, Noble implicitly teaches the introducing by birth into a target population an engineered organism comprising the preselected heritable trait, wherein the target population is either a captive population within a laboratory setting or a wild population, and wherein the introduction changes a genetic characteristic of the target population.
Regarding claim 2, Noble teaches i) delivering into a reproductive cell (e.g., a germline cell) of a captive individual of the organism a gene or gene allele that when expressed in a descendant of the captive female organism results in an engineered organism that exhibits the preselected heritable trait [Figure S3].
As discussed above for claim 1, the teachings of Noble a) to produce gametes comprising the preselected heritable trait [Figure S3] and b) of the trait spreading in a population to change a genetic characteristic within a target population/ alter a local population [title, abstract, page 7 ¶ 2] together necessarily require the birth of an engineered organism arising from the modified gametes, which also further necessarily requires impregnating a captive female of the organism to facilitate the development of the engineered gamete into an engineered adult organism capable of passing on its genes.
Noble does not teach whether the genetically engineered germline cells giving rise to genetically engineered gametes are male or female. However, editing either male or female germline cells will satisfy the claims as written. The editing of female germline cells represents a direct delivery of the gene or gene allele into a reproductive cell of a captive female. Alternatively, the editing of a male germline cell to produce genetically engineered sperm, which are then used to impregnate a captive female represents an alternative method for delivering the gene into a reproductive cell (e.g., oocyte) of a captive female in that the sperm will deliver its engineered genome into the oocyte upon fertilization.
As also discussed above for claim 1, releasing the impregnated captive female of the organism into the target population of organisms encompasses either introducing the impregnated captive female into a captive (e.g., laboratory) population or into a wild population. Noble teaches releasing engineered individuals comprising the preselected heritable trait into a wild population following a genetic engineering of the germ cells/ gametes, and thus necessarily implicitly teaches releasing/introducing the impregnated captive female into at least a target captive laboratory population and/or a target wild population of organisms.
Regarding claim 3, Noble teaches delivery of a gene or gene allele into a reproductive cell, along with propagation of that delivered gene within a population [title, abstract, page 7 ¶ 2, Figure S3], which as discussed above necessarily requires the impregnation of a female to birth a genetically engineered individual which can then mature and propagate the gene in the population, but does not teach specifically that the delivery of a gene or gene allele into a reproductive cell of a captive female of the organism itself impregnates the same captive female.
However, Taft teaches that in vitro fertilization (IVF) involves the incubation of oocytes with sperm, such that fertilization occurs and the sperm genome is inserted into the oocyte (e.g., two pronuclei are present in fertilized oocytes), followed by transfer of the embryos (e.g., cultured fertilized oocytes) generated thereby into the oviducts of pseudopregnant recipients for gestation [page 889 lines 22-33, 47-48, page 890 lines 1-2]. Taft further teaches that IVF involves fertilization of mature oocytes with capacitated sperm in a tissue culture dish, which can generate large numbers of cleavage-stage embryos without using a significant number of single-caged stud males for mating [abstract]. Therefore, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use IVF as a method of delivering a gene or gene allele into a reproductive cell of a female to generate large numbers of embryos from a limited number of males, wherein the process of IVF results in impregnating the recipient female.
Taft does not teach that the impregnated captive female is the same captive female from which the reproductive cell (e.g., oocyte) was obtained for the IVF procedure.
However, Brigham and Women’s Hospital teaches that the IVF process involves the steps of collection of the eggs from the ovaries of a female, mixing of sperm and egg to facilitate fertilization while in culture, and then placement of the embryos into the uterus of the female [page 1 lines 7-14]. As such, placing the IVF-generated embryo either into a surrogate female host as taught by Taft or into the same female from which the egg was retrieved as taught by Brigham and Women’s Hospital, thereby impregnating the recipient female, represents two alternative options. Therefore, it would have been obvious to an ordinarily skilled artisan to select from the limited number of options to use either a surrogate or the same female from whom the egg was obtained to gestate the genetically engineered organism.
Regarding claim 8, Noble teaches wherein the engineered organism is a male engineered organism by 1) teaching that the heritable trait is a male-linked sterile-daughter trait, wherein a male produces sons like himself and daughters that are sterile, such that only males can pass the trait on to descendants [Figure S10], and 2) that engineered males should remain in the population for an extended period once released [Figure S10].
Regarding claim 15, Noble teaches wherein the organism is a mammal (e.g., mouse) [Figure S1, S9, S10].
Regarding claim 52, Noble teaches wherein the preselected heritable trait is a sterile-daughter heritable trait [Figure S10].
Regarding claim 53, Noble teaches wherein the sterile-daughter heritable trait is generated by engineering a Y chromosome that disrupts an activity of a gene required for fertility of female offspring [page 12 ¶ 2, Figure S9, S10].
Noble does not specifically teach that the gene required for fertility of female offspring is located on an X chromosome.
However, Esvelt teaches a sterile daughter gene drive, wherein the sterile-daughter heritable trait is generated by engineering a Y chromosome that disrupts an activity of an X chromosome gene required for the fertility of female offspring (e.g., Y-Drive-SD system) [0030-0032, 0037-0038, 0082-0084, 0087, Figures 4, 5, 11, 12]. Esvelt further teaches that rats and other highly mobile species cannot be permanently eliminated barring total extinction of the species, but they might be controlled by periodically releasing a standard recoding drive in native populations and a Y-drive with sterile-daughter effect (Y-Drive-SD) through the invasive populations [0087, Figure 6]. Therefore, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use a gene drive system, such as the Y-Drive-SD taught by Esvelt, which generates a sterile-daughter heritable trait by engineering a Y chromosome that disrupts an activity of an X chromosome gene required for the fertility of female offspring to control a population of a highly mobile pest species.
Regarding claim 54, Noble teaches wherein the sterile-daughter heritable trait is generated by engineering a Y chromosome that produces a nuclease (e.g., Cas9 nuclease) carried in sperm of the engineered male organism and when present in a zygote, the nuclease cuts one or more female-specific fertility genes [page 3 ¶ 1, page 11 ¶ 1, page 12 ¶ 2, Figures S1, S9, S10].
Regarding claim 60, as discussed above, Taft teaches that IVF can generate large numbers of cleavage-stage embryos without using a significant number of single-caged stud males for mating [abstract]. Therefore, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use IVF as a method of delivering a gene or gene allele into a reproductive cell of a female to generate large numbers of embryos from a limited number of males.
Regarding claim 63, Noble teaching monitoring the spread of the Cas9 gene drive in order to identify the exact region that would be affected and adjusting the spread within a region by releasing wildtype organisms [page 11 ¶ 4]. Noble also teaches assessing the daisy gene drive systems in the field [page 12 ¶ 6].
Noble does not explicitly or specifically teach that the monitoring comprises detecting the preselected heritable trait (e.g., sterile-daughter gene drive) in an organism in the target population following the introduction by birth of the preselected heritable trait into the target population.
However, Turner teaches proposed post-release monitoring for genetically engineered olive flies comprising an OX3097D-Bol genetic construct encoding preselected heritable traits, including a female specific self-limiting trait (expression of tTAV protein) and a fluorescent marker (DsRed2) for use in field monitoring, wherein the DsRed2 fluorescent signal and/or the transgenes are detected in an organism in the target population following introduction of the preselected heritable trait into the target population [column 16 ¶ 5-12]. Turner further teaches that the post-release monitoring is part of risk assessment for use of the genetically engineered organism [abstract, column 5 ¶ 2, column 10 ¶ 3, Figure 1]. Therefore, an ordinarily skilled artisan at the time of filing would have been motivated to monitor the spread of the preselected heritable trait (e.g., sterile-daughter gene drive) by detecting the trait in an organism in the target population following the release of the trait into the target population to identify the region affected, adjust the spread, and aid in risk management.
Regarding claim 73, Turner further teaches that the post-release monitoring involves capturing organisms from the target population, wherein the capturing is aided in part by a predetermined spatial distribution of engineered organisms introduced (e.g., without or without the netted area) [column 16 ¶ 5-12]. Turner also teaches that immature stages may be monitored by sampling infested olive fruit, thereby teaching to monitor both male and female organisms since female offspring do not live past the larval stage [column 16 ¶ 3, 10].
Regarding claim 76, Noble, Taft, and Brigham and Women’s Hospital teach the limitations of claims 1-3. Together, as discussed above, they teach a method of altering a genetic characteristic of a target population of organisms of a species [Noble page 2 ¶ 2, page 4 ¶ 1], comprising:
obtaining one or a plurality of captive female organisms of a non-human species [Noble Figure S3, S9, S10; Taft page 886 line 24-25];
introducing a genetic element (e.g., a gene drive) from one or more male organisms of the species into the one or the plurality of the captive female organisms (e.g., through IVF), wherein each of the one or more male organisms exhibits one or more preselected heritable traits (e.g., a sterile-daughter heritable trait) [Noble page 12 ¶ 2, Figure S10; Taft page 889 lines 22-33, 47-48, page 890 lines 1-2]; wherein the introducing results in impregnation of at least one of the captive female organisms, and a descendant of the impregnated captive female organism exhibits one or more of the preselected heritable traits [Noble abstract, page 2 ¶ 1-2, page 11 ¶ 2-4, page 12 ¶ 4, Figure S10, Taft page 889 lines 22-33, 47-48, page 890 lines 1-2];
identifying one or more of the captive female organisms impregnated in (b) [Brigham and Women’s Hospital page 3 ¶ 2 teaches success rates for IVF, which inherently teaches to determine whether the female was successful impregnated by the IVF procedure]; and
releasing one or more of the identified impregnated captive female organisms into a target population of organisms of the species, wherein the presence of one or more descendants of the impregnated captive female organism alters a genetic characteristic of the target population [Noble abstract, page 2 ¶ 1-2, page 11 ¶ 2-4, page 12 ¶ 4, Figure S10].
As also discussed above for claim 1, releasing the impregnated captive female of the organism into the target population of organisms encompasses either introducing the impregnated captive female into a captive (e.g., laboratory) population or into a wild population. Noble teaches releasing engineered individuals comprising the preselected heritable trait into a wild population following a genetic engineering of the germ cells/ gametes, and thus necessarily implicitly teaches releasing/introducing the impregnated captive female into at least a target captive laboratory population and/or a target wild population of organisms.
Regarding claim 77, Noble teaches wherein the preselected heritable trait is a sterile-daughter heritable trait [Figure S10] arising from a gene drive inserted into the genome, which is therefore both a preselected phenotypic and a preselected genotypic heritable trait.
Regarding claim 81, Noble teaches the gene drive system in a rodent (e.g., mice) [Figure S10].
Given the motivation taught by Taft to use IVF as a method of delivering a gene or gene allele into a reproductive cell of a female to generate large numbers of embryos from a limited number of males, wherein the process of IVF results in impregnating the recipient female; the teachings of Brigham and Women’s Hospital to use the same female from whom the egg was obtained to gestate the genetically engineered organism; the motivation taught by Esvelt to use a gene drive system, such as the Y-Drive-SD taught by Esvelt, which generates a sterile-daughter heritable trait by engineering a Y chromosome that disrupts an activity of an X chromosome gene required for the fertility of female offspring to control a population of a highly mobile pest species; and the motivation taught by Turner to monitor the spread of the preselected heritable trait (e.g., sterile-daughter gene drive) by detecting the trait in an organism in the target population following the release of the trait into the target population to identify the region affected, adjust the spread, and aid in risk management; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the method of Noble to use IVF as a method of delivering a gene into a reproductive cell of a captive female, thereby impregnating the captive female, to use the gene drive system to disrupt a female fertility gene on the X chromosome, and to monitor the effects of the introduction in the population by detecting the presence of the transgene in a female of the population within a determined spatial distribution following the introduction with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-11, 95, 97-101, 10-104, and 106-110 of copending Application No. 16/331,772, hereinafter referred to as the ‘772 application, in view of Taft [2017, Cold Spring Harbor Protocols, 886-892].
The ‘772 application claims recite a method of preparing an engineered organism or a gene drive system, the method comprising a) crossing an organism of the strain with the engineered organism of the strain not released in the wild population or organisms of the strain to introduce copies of the gene cassette (e.g., a preselected heritable trait) into offspring of the crossed organism of the strain; and b) releasing the engineered organism of the strain into a wild population of organisms of the strain, and crossing organisms of the strain in the wild population with the released engineered organism of the strain to introduce copies of the DNA cassette (e.g., preselected heritable trait) into offspring of organisms of the strain in the wild population [claim 1]. As such, the ‘772 application claims introduction by birth of a preselected heritable trait into a target population which changes a genetic characteristic of the target population.
The ‘772 application further claims wherein the gene cassette disrupts a target gene which is required for one or both of viability and fertility of the organism of the strain. The ‘772 application claims do not specifically recite that the fertility gene disrupted is a female fertility gene. However, selecting a female fertility gene vs a male fertility gene represents selection from among a limited number of known options (e.g., 2), and as such would be obvious to an ordinarily skilled artisan.
The ’772 application does not specifically claim that the crossing of an organism of the strain with an engineered organism of the strain involves in vitro fertilization.
However, Taft teaches that in vitro fertilization (IVF) involves the incubation of oocytes with sperm, such that fertilization occurs and the sperm genome is inserted into the oocyte (e.g., two pronuclei are present in fertilized oocytes), followed by transfer of the embryos (e.g., cultured fertilized oocytes) generated thereby into the oviducts of pseudopregnant recipients for gestation [page 889 lines 22-33, 47-48, page 890 lines 1-2]. Taft further teaches that IVF can generate large numbers of cleavage-stage embryos without using a significant number of single-caged stud males for mating [abstract]. Therefore, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use IVF as a method of delivering a gene or gene allele into a reproductive cell of a female to generate large numbers of embryos from a limited number of males, wherein the process of IVF results in impregnating the recipient female. As such, it would have been obvious to an ordinarily skilled artisan at the time of filing the instant application to use the method of IVF for generation of a large number of engineered organisms.
Therefore, the ‘377 application claims encompass and render obvious the methods of claims 1-3, 8, 15, 52-54, 60, 63, 73, 76-77, and 81 of the instant application.
This is a provisional nonstatutory double patenting rejection.
Examiner’s Note
Co-pending U.S. Patent Application No. 17/776,762 claims a method of altering organisms of a species which comprises producing descendant offspring from an engineered male organism of the species, wherein the engineered male organisms of the species has a daughterless-male trait, which thus encompasses introduction by birth of an engineered organism comprising a preselected heritable trait, which thereby changes a genetic characteristic of a target population. No provisional non-statutory double patenting rejection over Application No. 17/776,762 is being applied because the co-pending application specifically claims a non-elected trait and does not presently claim the elected sterile-daughter trait.
Conclusion
No claim is allowed.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634