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 1-12 are pending in the application. Applicant’s election of Group I, claims 1-8, with traverse in the reply filed on Aug. 26, 2024 is acknowledged. Claims 9-11 are withdrawn for being drawn to non-elected subject matter, and claims 1-8 and 12 have been considered on the merits. All arguments have been fully considered.
Claim Objections
Claims 1-6 and 12 are objected to because where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m). Claim 1 and 12 each recites the cryptic term “E6.5.” If this is an abbreviation or reference to another term, then the full term needs to be spelled out at least once in the claim set. This might be remedied to be clearer if rewritten as a mouse embryo incubation/culture duration or “embryonic day 6.5 (E6.5).” Appropriate correction is requested.
Previous Rejections
Status of the rejections: the previous claim rejections under 35 USC 101 are modified in view of the claim amendments.
Claim Interpretation
In the claims, the composition is interpreted as a product-by-process with regard to the phrase “one or more fractions of a human plasma fractionation using Cohn method” and because there are no structural feature(s) recited in the claim or any implied limitation that would distinguish the recited composition made with a human plasma component(s) obtained by another process, e.g., without using the Cohn method. The process of obtaining the human plasma fraction is interpreted without limitation so long as the composition comprises a component(s) or composition(s) taken from human plasma to arrive at the claimed product. It is also noted that the term “Cohn method” consists of the method of separating blood plasma proteins disclosed in Cohn (Cohn et al., J Am Chem Soc., 68:459-75 (1946)) as defined by the amended instant Specification at pg. 4, 1st para.). Thus, under a broadest reasonable interpretation, the composition of claim 1 encompasses any composition comprising between 90-92.79% human serum albumins (HSA), 7.2-9.99% human alpha globulins, 0-2.79% human beta globulins, and 0.01-0.05% human gamma globulins, wherein the percentages are with regard to total proteins in the composition. This includes wherein each of the human proteins HSA, an alpha-globulin, a beta globulin, and gamma globulin are obtained in isolated form and combined into a single composition at the required amounts and percentages.
In claim 1, the term “embryo culture medium” is interpreted to encompass any medium suitable for culturing any embryo, such as KSOM, CRIaa, SOFaa, HTF, Tyrode’s medium, Whitten medium, Drosophila Schneider’s Medium, and commercially available variations like Global® LGGG and CaseBio®/EmbryoMax® KSOMaa media designed specifically for mammalian embryo culture.
In claim 12, the phrase “when a concentration of the composition in the embryo culture medium is 20% (v/v)” is interpreted as a contingent limitation to a process of intended use. Note, the broadest reasonable interpretation of a process claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met (see MPEP 2111.04).
Claim Rejections - 35 USC § 101 (modified)
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is to a natural product without significantly more. Based upon an analysis with respect to the claim as a whole, claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The claims are to a composition (STEP 1: YES)
The claims are directed to compositions consisting primarily of nature-based products, i.e., human plasma proteins (albumin and globulins) at defined protein percentages and relative ratio ranges, such as wherein the human plasma proteins have been partially purified from human plasma or isolated and recombined at said percentages.
The routine prior art Cohn method results in partial purification and isolation of serum protein components by producing intermediate compositions (e.g., a single fraction) comprising HSA between 90-96%, alpha and beta globulins between 3.5-9.99%, and gamma globulin between 0.01-0.5% of the total proteins in the composition, which includes wherein the alpha globulin makes up 7.2% or more of the total protein (instant Specification at pg. 3, last para.).
The art teaches that HSA, alpha globulin, beta globulin, and gamma globulin are each naturally occurring in human serum, albeit at different percentages than recited in claim 1, typically at about ~ 55% HSA, ~ 27% alpha and beta globulins, and ~ 18% gamma globulin for a healthy person (Vavricka et al., Digestion 79: 203-10 (2009) at Table 1). Thus, human serum is not the closest naturally occurring counterpart to the claimed composition; however the individual protein components each has a naturally occurring counterpart: human serum albumin, human alpha globulins, human beta globulins, and human gamma globulins. Because there is no evidence of a counterpart mixture in nature encompassed by claim 1, the closest counterparts to the claimed mixture are the individual components of the mixture, i.e., each naturally occurring protein by itself (MPEP 2106.04(c)(II)(a)).
The claims are directed to a product of nature (STEP 2A prong 1: YES).
Where a claim is to a nature-based product produced by combining multiple components, the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts (MPEP 2106.04(c)(I)(a)). Thus, this nature-based product is analyzed to determine whether the claimed composition possesses markedly different characteristics in combination from merely the individual naturally occurring counterparts.
The claimed composition differs structurally from any naturally occurring composition regarding the percentages of the proteins: HSA, alpha globulin, beta globulin, and gamma globulin, but this alone is not a “markedly” different characteristic. However, the claimed composition is further limited to wherein, upon adding the composition to an embryo culture medium, it has the ability to allow at least 60% of a population of embryos cultured in the medium to “complete hatching” at E6.5 days and to allow at least 70% of said hatched embryos “to adhere to a surface of a culture plate.”
The prior art teaches that embryo culture medium supplemented instead with human serum (fetal cord) can result in a mouse embryo hatching rate of over 80% (Ogawa and Marrs, Fertil Steril 47: 156-61 (1987) at EXPERIMENT 1, Fig. 1), and that mouse embryo populations can be hatched at high rates (70%) in the absence of any human serum component or supplementation with just HSA (e.g., 100% recombinant HSA added at 0.05 mg/mL) (Otsuki et al., Syst Biol Reprod Med 59: 48-52 (2013) at Table 1). Regarding culture plate adherence, the prior art teaches over 80% adherence of hatched mouse embryos can be achieved by a medium lacking any human serum supplement when the plate surface is coated with a fibronectin (Yelian et al., Mol Reprod Dev 41: 435-48 (1995) at Table 1). Therefore, the balance of the evidence points to the absence of any markedly different characteristic as the recited effects can be achieved with media supplemented with human serum.
Thus, when examining Step 2A prong 2, the answer is ‘NO’ because the claimed invention does not integrate the judicial exception into a practical application. There are no other additional elements recited in the claim that would amount to significantly more than the judicial exceptions. Furthermore, there is no evidence that the further purification and/or processing recited in claims 2-8 used to make the claimed product results in any property or structure that is not attributable to one or more of the unmodified naturally occurring components’ individual or collective functions, i.e., human alpha globulin being at a level of 7.2-9.99 % of the total protein and/or HSA at less than 92.8% and/or human alpha globulin being around 9 mg/mL and HSA being around 100 mg/mL. Instead, the recited combination of natural components does not change the nature-based components (human serum HSA and globulins) in a significant or meaningful way to amount to more than the judicial exception. Regarding claims 4-6, further processing besides fractionating of any combination of dilution, clarification, diafiltration, nanofiltration, concentration by ultrafiltration, sterilization, lyophilization, heat treatment (pasteurization), gamma irradiation, and/or elimination of pathogens does not introduce any markedly different characteristic to the compositions according to claims 1-3.
Response to Arguments
Applicant’s remarks filed 3/3/26 were full considered. Applicant traverses the section 101 patent eligibility rejections in the response at pg. 5-8 by arguing the product of claim 1 having partially purified, plasma-derived components in specific ratios do not exist in nature but instead requires a human intervention of purification to an intentionally enriched level of protein components, and thus amounts to significantly more than a natural product due to markedly different characteristics of composition and structure when compared to human plasma. These arguments were not found persuasive.
Claim 1 is directed merely to a composition (product meant for supplementing an embryonic culture medium) that encompasses four or more naturally occurring human plasma proteins: HSA, alpha globulin(s), beta globulin(s), and gamma globulin(s) in a range of unnatural percentages compared to natural human plasma or blood. The instant application fails to disclose if any structural characteristics of the naturally occurring counterparts, e.g., isolated/purified human serum proteins are markedly different. Rather, Applicant clearly argues there is a markedly different function resulting from the chosen level of naturally occurring proteins in the claimed composition, implicitly as a collective effect of the relative amounts of the recited serum proteins or possibly even due to unrecited minority components in the Cohn fraction(s).
The claimed composition differs structurally from any naturally occurring composition regarding the percentages of the proteins: HSA, alpha globulin, beta globulin, and gamma globulin, but this alone is not a “markedly” different characteristic. The mere fact that the composition is structurally different from any naturally occurring composition would not render it patent eligible. As in the “Guidelines” (Nature Based Products 101 Examples) cited in the response, this most resembles Example 6, claim 1, and Example 9, claim 4, where a mixture of different species of purified cells or an isolated human cell population is not automatically patent eligible subject matter just because it is mixed and/or “isolated” by human interventions.
However, the claimed composition is further limited to having an inherent characteristic, the capability wherein, upon adding the composition to an embryo culture medium, the medium then has the ability to allow at least 60% of a population of embryos cultured in the medium to “complete hatching” at E6.5 days and to allow at least 70% of said hatched embryos “to adhere to a surface of a culture plate.” The response and instant application purports to show that a “Composition III” encompassed by claim 1 and having about 91% HSA (seroalbumin) and at least about 7.2% alpha globulins (5.4+1.8%) but with unknown other constituents provide advantageous unexpected benefit in culturing mouse embryos when used to supplement KSOMaa medium in lieu of 5 mg/mL BSA (instant pg. 7, FIG. 1-2; Table I), possibly due solely to the presence of human alpha globulin at a level of 7.2-9.99 % of the total protein in the composition prior to addition to the embryo culture medium (Response filed 3/3/26, at pg. 6); however the amounts of other proteins in the composition, e.g., maintaining the HSA at less than 92.8% and/or around about 108 mg/mL, may also contribute to this effect.
There is a lack of evidence that the claimed product has any markedly different structural/functional characteristic that would not be present in human serum or purified products of human plasma simply recombined in various ratios, e.g., non-naturally occurring ratios responsible for the supposedly markedly different function from a mere mixture of natural human protein counterparts within the same ranges of percent component per total protein (e.g., ≥ 7.2% alpha globulin or HSA < 92.8%, i.e. about 7.2-9.99% alpha globulin and about 90-92.7% HSA). Instead, arguments were made drawn from a comparison data of two human-made derivates of human plasma of differing ratios (Composition I and Composition III) used as intermediates in the creation of mammalian embryo culture media to identify an intended use difference between two patent-ineligible compositions or purported unexpected effects as compared to a single alternative composition known in the prior art, bovine serum albumin (BSA).
One question is whether the purported unexpected result as secondary indicia for a 103 analysis as previous put forth on the record is a markedly different characteristic in the 101 analysis. Based on the current evidence, the answer is no as set forth in the rejection above. Furthermore, even if there was a markedly different characteristic as argued, based on the evidence of record, this markedly different function is not commensurate with the full scope of the claims because the exemplary Composition III is not representative of the full scope of the claims as explained in the rejections below. Importantly, it is not of record what Cohn method fraction(s) were used to make Composition III, if any, as Applicant’s arguments only address generic claim 1, which at least encompasses all the species of claims 2-6. Thus, the instant application provides evidence that certain, but unknown to the record, isolated fraction(s) or mixture(s) thereof of the Cohn method applied to human plasma is useful when added to mammalian embryo culture medium for improving mouse embryo hatching rates, adhesion to culture plates, implantation in collagen hydrogels, and survival in culture as disclosed by in the specification.
The recited combination of natural components does not change the nature-based components (human serum HSA and globulins) in a significant or meaningful way to amount to more than the judicial exception, especially without the purported markedly different characteristics fully mapping to the broad scopes of all the claims and the mystery as to the nature of Composition III with regard to precise Cohn fractions.
While Applicant’s evidence and arguments suggest that a mammalian embryo culturing medium comprising Cohn method fraction(s) restricted to alpha globulin at 7.2% or more of the total proteins and HSA at less than 92.8% of the total proteins in the composition might have markedly different characteristics than naturally occurring counterparts, this is not what is now claimed due to overbreadth (see 112A rejection below). Applicant argues that the claimed nature-based composition is markedly different from natural counterparts due to providing the function of improved mouse embryo viability and hatching compared to similar Cohn method fraction derived composition (Composition I) having alpha globulin at 1.1% and HSA at 98.9% (instant specification pg. 7, lines 11-21; FIG. 1; table I). However the comparison is not commensurate in scope with the claims, which cannot be used for improving mouse embryo viability and hatching over the full scope of claims 1-8, e.g., any composition comprising HSA between 90 % and 96 % of the total proteins in the composition, alpha and beta globulins between 3.5 % and 9.99 % of the total proteins in the composition, and gamma globulin between 0.01 % and 0.5 % of the total proteins in the composition, wherein the composition comprises said alpha globulin at 7.2% or more of the total proteins in the composition. Rather, Applicant has shown that a KSOMaa basal medium (potassium simplex optimized medium with amino acids) supplemented with the claimed product at certain ranges might comprise the inherent capability that is a markedly different characteristic for a 101 analysis.
Applicant is invited to provide further evidence that a markedly different characteristic is either inherently present in the claimed product or to expressly require the characteristic to be present using a claim limitation(s). Ideally, each purified human protein would be tested separately and compared to the claimed combination in the Cohn fraction(s), such as when used as a media supplement. Applicant is further encouraged to amend the claims to tightly tie the markedly different characteristic to the scope of what is being claimed to ensure the purported markedly different characteristic is always present, i.e. claim scope is commensurate.
Claim Rejections - 35 USC § 112(a) - Written Description (new)
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 1-8 and 12 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.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
The claims are directed to a product intended for use as a media additive during embryo culturing through hatching and beyond. The product (media supplement) is a composition comprising between 90-92.79% human serum albumins (HSA), 7.2-9.99% human alpha globulins, 0-2.79% human beta globulins, and 0.01-0.05% human gamma globulins, wherein all these percentages are with regard to total proteins present in the composition and wherein the composition is made with one or more fractions of the Cohn method applied to human plasma. The claims are directed to a product intended for use in a process. This process comprises adding the composition to an embryo culture medium and results in (1) at least 60% of embryos “hatching” at 6.5 days after fertilization (e.g., wherein a plurality of embryos are incubated in the embryo culture medium comprising the composition) and (2) at least 70% of the “hatched” embryos adhering to a surface of a culture plate (e.g., a plate or well(s) of a plate containing the embryos in the medium comprising the composition).
The claims are broad in that the term embryo encompasses any type of embryo and the term hatching is not limited or defined in any manner whereas the claims are narrow in that the specific method results must occur, including the hatching completion limitation is defined using a specific number of days after fertilization and the hatching moment is defined as exactly at 6.5 days.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described. In the instant case, the specification fails to provide a single working example of wherein the embryos are not mouse embryos, and thus only one exemplary species of embryo is disclosed. Also, the specification fails to provide a single working example of wherein 60% or more mouse embryos all hatch at 6.5 days after fertilization, instead showing one example whereby a 3 day culturing ending at day E6.5 provides for more than 60% mouse hatching.
The prior art teaches that embryos exist for millions of different species, including flowering plants, fish and insects. While the prior art teaches mouse embryo hatching means the process of a blastocyst breaking out of the zona pellucida and this shared by most placental (eutherian) mammals (see Leveille, M. C., et al., J Assist Reprod Genet. 9: 45-52 (1992) at pg. 46, left col.), the prior art does not teach the full scope of the term “hatching” as used in claim 1 with regard to any embryo or occurring completely and precisely at 6.5 days after fertilization for any mammal other than a mouse absent evidence to the contrary (e.g., an elephant or blue whale).
The instant application provides evidence from a single working example using a single species termed “composition III,” which when combined at a final concentration of 5 mg/mL of HSA allowed for 62% of mouse embryos incubated in the medium to completely hatch by day E6.5 when the incubation was started at day E3.5 (Example 2, FIG. 1; pg. 5, lines 21-25). If mouse embryos are cultured in the medium from E3.5 to E7.5, then 73% adhered to a culture plate (Example 3, FIG. 2).
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of the full scope of the claimed methods encompassed by the broad term “embryos” encompassing invertebrate embryos and embryos of species that do not hatch or whose embryonic timeline differs from the mouse at day E6.5. The dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim for all parameters.
Minimum composition concentration and duration to reach compete hatching and adherence
In the instant case, the claims are broad in that complete hatching is required at 6.5 days after fertilization but there is no limitation as to how long the embryos are contacted with the composition and/or embryo culture medium, if at all. Similarly, the claims are also broad in that hatched embryos adherence to the surface is required at 70% of the total of hatched embryos present but there is no limitation as to when the embryos are contacted with the composition, embryo culture medium, and/or culture plate, if at all, such as continuously from before to after hatching or after day 6.5. Importantly, the dosage/concentration of the composition exposed to the embryos is unlimited, with no minimum.
While the specification describes culturing/incubating a plurality of mouse embryos in a medium comprising “composition III” for 4 days in the presence of a culture plate having a surface to achieve the results recited in claim 1, the application lacks sufficient disclosure as to produce the recited result if the toral duration is less than 4 days (Example 2-3). Furthermore, the application lacks sufficient disclosure as to produce the recited result if the amount of the composition differs from 5 mg/mL based on the HSA component as the only empirical evidence provided is at this single concentration.
Note, if the number of embryos is 2, then 100% of the embryos must complete hatching at 6.5 days to reach the at least 60% threshold. Similarly, if the number of hatched embryos is 3 or less, then 100% of the hatched embryos must adhere to the surface to reach the at least 70% threshold. There is no working embodiment demonstrating 100% hatching or 100% adherence, as needed for very small pluralities of embryos, or more than 62% hatching and 73.1% adherence as needed for embryo pluralities less than 18 embryos.
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of a method of predictably producing (1) at least 60% of embryos “hatching” at 6.5 days after fertilization and (2) at least 70% of the “hatched” embryos adhering to a surface of a culture plate over the scope of any embryo or at exactly E6.5. Additionally, the skilled artisan could not rely upon the disclosure in the specification sufficiently describes that Applicant was in possession of a method of predictably producing (1) at least 60% of mouse embryos hatching within 6.5 days after fertilization and (2) at least 70% of the hatched mouse embryos adhering to a surface of a culture plate over the scope of generically adding the composition to an embryo culture medium, providing mouse embryos and waiting until day 6.5 post-fertilization with the hope of 60% embryo hatching or 70% of hatched embryo attachment with regard to effective amount of composition present and sufficient incubation duration of the embryos with the composition and medium in a culture plate at physiological conditions. Adequate written description requires more than a mere statement of an intended result of practicing the invention and reference to the broadly claimed method described only at a high level of generality.
35 USC § 112(a) – Scope of Enablement (new)
Claims 1-8 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while enabled for wherein the embryos are mouse embryos, there are at least 18 embryos such that at least 11 completely hatch by E6.5, and of the hatched embryos at least 8 of the 11 adhere; the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the full scope of claim 1 which is unlimited in the embryo type, the hatching conditions, the adhering conditions and the minimum amount of the composition in the medium.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). 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 weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention:
Claim 1 is directed to a product (a composition) for use in embryo culturing process whereby the composition is capable of, after addition to an embryo culture medium comprising a plurality of embryos in a culture plate, of producing (1) at least 60% of embryos “hatching” at 6.5 days after fertilization and (2) at least 70% of the “hatched” embryos adhering to a surface of the culture plate.
The state of the art:
The prior art teaches media for mammalian embryo culture comprising human serum albumin, alpha-globulin, and beta globulins, such as at 4.4-5 mg/mL HSA and 88% HSA and 12% globulins (Morbeck et al., J Assist Reprod Genet 31: 1703-11 (2014), IDS ref.; at pg. 1704, left col., 2nd para. and right col., 1st para.; pg. 1708, right col., 2nd para.). The prior art teaches methods of culturing, hatching and attaching mouse blastocysts/embryos to culture plates made of optical plastic (see Park et al., Clin Exp Reprod Med 41: 68-74 (2014) at abstract; Bedzhov et al., Nat Protoc 9: 2732-9 (2014) at abstract; pg. 2731, right col., 1st para.); however the prior art is silent as to any method specifically using one or more Cohn fractions to promote mouse embryo hatching and hatched embryo adherence wherein the human alpha globulin protein percentage is between 7.2-9.99% of total proteins in the fraction.
Therefore, the disclosure provided by the applicant in view of prior art must encompass a wide area of knowledge to a reasonably comprehensive extent so that one of the ordinary skills in the art would be able to practice the invention without any undue or reasonable burden being on such artisan.
The amount of direction and guidance and working examples provided by Applicant:
The instant application provides a single working example using KSOMAA (Millipore, USA) supplemented with “composition III,” which when combined at a final concentration of 5 mg/mL of HSA allowed for 62% of mouse embryos incubated in the medium to completely hatch by day E6.5 when the incubation was started at day E3.5 (Example 2, FIG. 1; pg. 5, lines 21-25). If mouse embryos are cultured in the medium from E3.5 to E7.5, then 73% adhered to a culture plate (Example 3, FIG. 2). Although the exact composition of “composition III” is unknown/undisclosed, the majority components are shown in Table I as a mean for n=3.
From the empirical data of this single working example, it is not necessarily predictable that at least 60% of mouse embryos will completely hatch at 6.5 days after fertilization or that at least 70% of the hatched embryos will adhere to a plate surface. The claimed process lacks limitations as to when/if the embryos are contacted with composition and/or embryo culture medium and for how long to ensure complete hatching and hatched embryo adherence.
The instant application lacks any guidance on how to alter the composition concentration in the medium and still ensure the recited results occur by performing the process; however, applicant is invited to furnish evidence the contrary. Regarding claim 12, while there is evidence in the working example that a concentration of 5 mg/mL is operational, this would be equivalent to 20% (v/v) only if the original composition had a HSA concentration of about 25/mg/mL (g/L), which is not the case for the working example using “composition III.” The instant application also lacks any guidance on how to adapt this to non-mouse embryos, such as insect or platypus embryos.
Thus, neither the instant application nor the prior art describes a method enabled over the full scope of any of the claims and there is little to no guidance as to how to adapt the single working example to the breadth in the scopes of (1) any embryo type, (2) any hatching conditions, (3) any adhering conditions, (4) any amount of composition in the medium, (5) any numerical plurality of embryos while also ensuring the narrow results of at least 60% hatching and 70% adherence as well as all hatching completing exactly at 6.5 days. This leaves the unguided skilled artisan only with the teachings of the closest prior art.
The quantity of experimentation needed to make and/or use the invention:
Extensive experimentation would be required to determine how to achieve both at least 60% hatching at 6.5 days after fertilization and at least 70% adherence of hatched embryos over the full scope of any embryo and without a minimum amount of the composition in the medium. The science of embryo culture had not evolved such that without guidance or working examples in the specification, one of skill in the art could predictably perform claim 1 across its full scope without undue and unreasonable experimentation.
In summary, the claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement to a person skilled in the art, to which it pertains or with which it is most nearly connected, to perform the claimed process across its full breadth. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of multiple features along with two high percentage results occurring, undue and unreasonable experimentation would have been 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 1-8 and 12 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 pre-AIA the applicant regards as the invention.
Claim 1 recites “the embryos,” which lacks sufficient antecedent basis and is also ambiguous. Does the embryo culture medium or composition comprise the embryos or does the process comprise an embryos adding step? Claims 2-8 and 12 are included in this rejection due to their dependence from claim 1.
Claim 1 and 12 recites “(E6.5)” which renders the claim indefinite where language set off within parenthesis is unclear as to whether this is a limitation, optional feature, or merely an initialism/abbreviation for something. Claims 2-8 are included in this rejection due to their dependence from claim 1.
Claim 1 and 12 recites the phrase “a surface of a culture plate,” which is incoherent and ambiguous as it is unclear how/when the culture plate is incorporated into the recited process involving adding, hatching, and adhering. Claims 2-8 are included in this rejection due to their dependence from claim 1.
Claim Rejections - 35 USC § 112(d) (new)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 12 attempts to narrow the scope of claim 1 to wherein the concentration of the composition in the embryo culture medium is 20% (v/v); however, the phrase “when a concentration of the composition in the embryo culture medium is 20% (v/v)” is interpreted as a contingent limitation that need not necessarily occur, whereas both “(a) at least 60% of the embryos reach complete hatching at 6.5 days after fertilization” and “(b) at least 70% of the hatched embryos adhere to a surface of a culture plate” are already limitations required by claim 1, regardless of the concentration of the composition in the embryo culture medium.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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/ERIC J ROGERS/
Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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