DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-10,24-25,27-32 and 34 are pending and under consideration.
Claim Objections
Applicant is advised that should claim 25 be found allowable, claim 29 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 101
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 24 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The embryo of claim 24, although made in vitro, encompasses human embryos. A human being is non-statutory subject matter. See 1077 O.G. 24, April 21, 1987.
Claims 24 is rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 24 does not recite something significantly different than a law of nature/natural principle.
Claim 24 is rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claims as a whole, claim(s) 24 is determined to be directed to a natural product and does not recite something significantly different than the natural product. The rationale for this determination is explained below:
Claim 24 is directed to an embryo made by the method of claim 1. Claim 1 is encompasses an in vitro fertilization method that includes steps of assaying the culture media, which does not affect the structure of the embryo. The claim then requires selecting an embryo and implanting the embryo into a surrogate mother. The embryo can be an animal of any species that fails to differ from an animal in nature, whether conceived naturally or through IVF.
The claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) that the embryo is obtained through a process that does not result in a mammalian embryo that differs in any way from that found in nature. This judicial exception is not integrated into a practical application there are no additional elements that add a meaningful limitation to the product because assaying the media surrounding the embryo fails to alter the embryo itself. Further, IVF embryos also fail to differ in any meaningful way from their natural counterparts. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. More detailed analysis is set forth below.
The Office published Office’s new guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published December 16, 2014. Applicant is directed to the Federal Register at page 74621.
The Office published Office’s new guidance document entitled 2019 Revised Patent Subject Matter Eligibility Guidance, published January 7, 2019. Applicant is directed to the Federal Register, Volume 4, No. 4, pages 50-57 at page 74621.
The Office published the guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published December 16, 2014.
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Step 2A was revised to include two prongs (Federal Register / Vol. 84, No. 4 / Monday, January 7, 2019):
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Step 1: The claim is directed to a composition of matter (cells and an inhibitor; Step 1: Yes).
Step 2A – Prong 1: Examiners evaluate whether the claim recites a judicial exception. The composition of matter (an embryo) is directed to a natural phenomenon (Step 2A, prong 1: Yes). MPEP §2106.04(b)(I) which shows that isolated DNA, cloned animals are considered natural phenomenon, for example.
Step 2A- Prong 2: Examiners evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception. This judicial exception is not integrated into a practical application because the do not recite additional elements that integrate the judicial exception into a practical application as no other elements are recited.
Step 2B- Step 2B the claim is evaluated as to whether it recites additional elements that amount to significantly more than the judicial exception.
The claim(s) are directed to a composition of matter (Step 1). This composition of matter is directed to a natural phenomenon (Step 2A) without additional elements (Step 2B). The claimed composition of matter fails to differ markedly from that found in nature. Markedly different characteristics can be expressed as the product' s structure, function, and/or other properties. In accordance with this analysis, a product that is purified or isolated, for example, will be eligible when there is a resultant change in characteristics sufficient to show a marked difference from the product' s naturally occurring counterpart. The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties. Non-limiting examples of the types of characteristics considered by the courts when determining whether there is a marked difference include: Biological or pharmacological functions or activities; Chemical and physical properties; Phenotype, including functional and structural characteristics; and Structure and form, whether chemical, genetic or physical. It is concluded, here, that the claimed natural products are not markedly different from their natural counterparts as a result of their being subject to an assay of their media or their derivation from an in vitro fertilization event.
Step2B then asks if the claim(s) include additional elements that are sufficient to amount to significantly more than the judicial exception.
Based on the guidance, The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to significantly more than the judicial exception itself. Limitations that may be enough to qualify as ‘‘significantly more’’ when recited in a claim with a judicial exception include: Improvements to another technology or technical field; improvements to the functioning of the computer itself; applying the judicial exception with, or by use of, a particular machine; effecting a transformation or reduction of a particular article to a different state or thing; adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application; or other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
Limitations that were found not to be enough to qualify as ‘‘significantly more’’ when recited in a claim with a judicial exception include: Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer; simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well-understood, routine and conventional activities previously known to the industry; adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea; or generally linking the use of the judicial exception to a particular technological environment or field of use.
Claim Rejections - 35 USC § 112
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 8-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 is unclear which primers are included in each set. There are commas between sets as well as within sets. The claim would be more clear if each set were either enumerated or separated with a semicolon. Claims 9 and 10 are unclear based on their dependency from claim 8.
Claims 25 ana 29 are unclear with regard to what “value based on a genotype-based value model” means.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 24 is/are rejected under 35 U.S.C. 102a1 and a2 as being anticipated by USPGPUB 20190075769.
Claim 24 is drawn to an embryo produced according to the method of claim 1. Claim 1 requires combining male and female gametes in vitro, culturing the embryo, carrying out an assay on the media of the embryo whereby the embryo is not changed by the assay or by selecting the embryo based on the outcome of the assay, and implanting the embryo into a surrogate mother.
‘769 teaches a method of making an animal comprising combining male and female gametes in vitro to form and embryo. The IVF was performed to produce F1 cross-breed embryos where the F0 parents were selected based on one or more improved performance characteristics. Para 8 teaches, “…the invention provides methods of breeding cattle comprising: generating an embryo from male and female F0 gametes, wherein one or both of the male and female F0 gametes is from an F0 individual selected based on performance of prior F1 progeny resulting from a cross of gametes from the F0 individual…”. The embryos are cultured for a period of time before implantation.
Because the assay and choosing the embryo does not alter the embryo, the method of ‘769 creates an embryo that is indistinguishable from that made by the method of claim 1.
Claim(s) 1-3,5-7,24-25,27-32,34 is/are rejected under 35 U.S.C. 102a1 and a2 as anticipated by USPGPUB 20190002985.
Claim 1 is drawn to a method of making an animal or cell line comprising combining male and female gametes to generate an embryo, adding an amplification reaction mix to cell-free DNA in the medium of the embryo, determining if the primers in the amplification mix amplify a target trait-related locus based on a turbidimetric, colorimetric or fluorescent indicator and selecting an embryo based on the outcome of the amplification and implanting the selected embryo or generating a cell line from the embryo based upon the amplification result.
‘985 relates to non-invasive embryo selection in IVF and teaches determining the quality or other traits (such as sex) of an embryo by determining the level of cell-free nucleic acids and/or determining the presence of at least one nucleic acid sequence in the nucleic acid extraction to select an embryo for implantation. ‘985 teaches that the methodology can be applied to humans as well as other mammals, including cows.
Specifically, ‘985 claims
An in vitro non-invasive method for selecting a human embryo and subsequently implanting said embryo in a woman undergoing in vitro fertilization, said method comprising the steps consisting of: i) providing a sample of the culture medium where the embryo is grown; ii) extracting the cell free nucleic acids from the sample; iii) determining the level of cell free nucleic acids in the nucleic acid extraction; iv) comparing the level determined at step iii) with a reference value, v) selecting the embryo when the level determined at step iii) is lower than the reference value; and vi) implanting the embryo selected in step v) in said female. (claim 7).
Furthermore, para 27 teaches:
Real-time quantitative or semi-quantitative RT-PCR is preferred. In a particular embodiment, the determination comprises hybridizing the sample with selective reagents such as probes or primers and thereby detecting the presence, or measuring the amount of the nucleic acid….Nucleic acids exhibiting sequence complementarity or homology to the nucleic acid of interest herein find utility as hybridization probes or amplification primers.… In certain embodiments, it will be advantageous to use nucleic acids in combination with appropriate means, such as a detectable label, for detecting hybridization. A wide variety of appropriate indicators are known in the art including, fluorescent, radioactive, enzymatic or other ligands (e.g. avidity/biotin).
‘985 teaches preimplantation genetic diagnosis (para 4) using cfDNA (para 6). Specifically, ‘985 teaches combining male and female gametes in vitro to form an embryo at para 43 (Conventional IVF or ICSI was used…). ‘985 taught culturing the embryo for a time sufficient for cell-free DNA to accumulate in the medium (The embryos were placed into extended culture media and continued until day 5…Quantification of the cfDNA in Culture Media…” (para 43-44). ‘985 teaches adding the medium to an amplification reaction mix comprising primers targeted to a trait -related locus and a fluorescent indicator (see para 50-53). ‘975 teaches that the amplification reaction with appropriately designed primers can detect the presence of a single nucleotide mutation (para 53).
With regard to selecting an embryo and implanting the embryo (claim 1) and selecting the embryo if the trait-related locus is amplified (claim 2) or not amplified (claim 3), ‘985 states “Accordingly the method of the invention is able to combine pre-implantation genetic testing and selection of the best embryo that is able to give rise to pregnancy.”
Beginning at para 63, ‘985 teaches using the cfDNA in embryo culture medium to detect make embryos by using primers specific to TSPY (claims 5-7). ‘985 teaches that TSPY1 may prove to be a valuable biomarker of embryo sex determination by amplifying the gene from cfDNA in the culture medium.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over USPGPUB 20190002985 in view of WO2020/061637.
‘985 meets the limitations of claim 1 as set forth above. ‘985 does not teach LAMP as a means of amplifying the cfDNA.
However, ‘637 also relates to noninvasive preimplantation genetic screening using DNA from cell-free medium. ‘637 teaches culture of embryos in vitro for 4-6 days, obtaining the cell-free medium containing DNA in which the embryo was cultured, and assessing the DNA for pre-implantation genetic testing. At para 59, it is taught that the DNA can be amplified using LAMP (claim 4) and incorporates by reference, Tomita (2008, Nature Protocols, 3:877-882). Tomita teaches LAMP as a simple, rapid, specific and cost-effective nucleic acid amplification method compared to PCR for genetic testing and that LAMP can be coupled to a fluorescent indicator (claim 1).
It would have been obvious at the time of filing to carry out the method of IVF to select for a trait using the cfDNA in the embryo culture media as taught by ‘985 and ‘637 using LAMP as taught by ‘637 to arrive at the invention as claimed. One would have been motivated to make such a combination as ‘985 teaches that in addition to being a means of assessing embryo quality, analysis of the cfDNA can allow for selection of mutations, SNP or sex-linked markers to select for sex or mutations and ‘637 teaches LAMP as a highly efficient means for amplifying desired loci. One would have had a reasonable expectation of success in using LAMP in the amplification using cfDNA because trait-related gene sequences, including those for sex-determination, were known at the time of filing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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