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 1-3, 6-8, 11, 15-16, 22, 24, 26, 33, 35, 37-38, 40, 43, 45-46, 48, 50-52, 56 and 59-60 are pending.
Claim Objections
Claim 22 is objected to because of the following informalities: In claim 22, line 5, “estrodiol” should read “estradiol”. Appropriate correction is required.
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 22, 16 and 43 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 16 contains the trademark/trade name KnockOut. Claims 22 and 43 contain the trademark/trade name GlutaMax. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe a serum replacement and a medium supplement. Accordingly, the identification/description is indefinite.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 60 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). An excerpt from the specification: “The methods and compositions herein described can be applied to embryos from any suitable mammalian species, such as: primates, including humans, great apes (e.g. gorillas, chimpanzees, orangutans), old world monkeys, new world monkeys; rodents (e.g. mice, rats, guinea, pigs, hamsters); cats; dogs; lagomorphs (including rabbits); cows; sheep; goats; horses; pigs; and any other livestock, agricultural, laboratory or domestic mammals.”
Claim 60 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim recites: A synthetic embryo obtained by the method of claim 1. This judicial exception is not integrated into a practical application because:
Step 1: Claim 60 recites an embryo, obtained by the synthetic method of claim 1. Such embryo is a composition of matter and thus is a category of patentable subject matter.
Step 2A, prong 1: the obtained embryo has the same structure that exists in nature. The embryos then are determined to be the judicial exception, as it is a natural phenomenon.
Step 2A, prong 2: There is nothing in the claim to integrate this embryo into a practical application. The claim is drawn to the embryo itself.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because:
Step 2B: There are no additional elements, but fishing through the method of making, there are implications that the overexpressed genes may be delivered by plasmids which are lost during the process of multiplying, or may be activated by the use of activators of CDX transcription, which may be done by, e.g. exposure to FGF. The specification is open-ended on how the ESCs overexpress the transcription factors e.g., Applicant's PGPub 2024/0124835, in paragraph 6, comparing the first mention of how overexpression is made, it is first stated that it is done, then says "In some embodiments" it is done by "In some embodiments, the method further comprises: generating the mammalian ESC overexpressing GATA transcription factor and the mammalian ESC overexpressing CDX2 transcription factor by contacting a mammalian ESC carrying an inducible Gata gene and a mammalian ESC carrying an inducible Cdx2 gene with an inducer." Further even for the genetic transfection subject matter, the vector may be plasmid, and plasmids are known to be lost with cell division. Thus, by way of open-ended language, the claims embrace the genera of overexpressed transcription factors, by way of exposure to a compound that causes their overexpression, and also for episomal vectors that are lost over time. It is well known that FGF causes overexpression of CDX. Therefore, compounds can be used to overexpress these transcription factors to obtain the embryo. However, once the embryo is obtained, it would still have the same structure as the natural embryo, as the factor or plasmid utilized may be lost from the embryo.
Thus, as a whole, the claim embraces embodiments that also exist in nature, and do not add any new properties and are not integrated into a larger whole that is distinct from nature. As such, the claim is properly rejected for being drawn to a natural phenomenon.
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.
Claims 1-3, 6-8, 11, 15-16, 22, 24, 33, 35, 37-38, 40, 43, 45-46, 48, 51-52, 56 and 59 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tarazi et al. (Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs, Cell. 2022;185(18):3290-3306.e25., cited on IDS), hereinafter Tarazi. The references mapped to the prior art are in bold print and parenthesis (), within the claims when present.
Regarding claim 1, Tarazi teaches a method of generating a synthetic embryo in vitro, the method comprising: (a) co-culturing a wild-type mammalian embryonic stem cell (ESC), a mammalian ESC overexpressing CDX2 transcription factor, and a mammalian ESC overexpressing GATA transcription factor under a condition allowing the ESCs to self-assemble into a gastrulating embryo structure (Abstract); and (b) culturing the gastrulating embryo structure in a post-implantation culture medium under a condition allowing the gastrulating embryo structure to develop into a synthetic embryo (Figure 2, “Naïve ESC derived sEmbryos complete gastrulation..” ,p. 3293)
Regarding claim 2, Tarazi teaches the method of claim 1, the GATA transcription factor is GATA4 (Methods – “Generation of iGATA4…” , p. 3306.e6).
Regarding claim 3, Tarazi teaches the method of claim 1, further comprising: generating the mammalian ESC overexpressing GATA transcription factor and the mammalian ESC overexpressing CDX2 transcription factor by contacting a mammalian ESC carrying an inducible Gata gene and a mammalian ESC carrying an inducible Cdx2 gene with an inducer (Generation of iGATA4…”, p. 3306.e6).
Regarding claim 6, Tarazi teaches the method of claim 1, wherein the ESCs are co-cultured for up to 6 days (Figure 2A).
Regarding claim 7, Tarazi teaches the method of claim 1, wherein the gastrulating embryo structure resembles an E6.0-E7.5 natural embryo structure, optionally an E6.0-E6.5, E6.5-E7.0, or E7.0-E7.5 natural embryo structure (Figure 2A).
Regarding claim 8, Tarazi teaches the method of claim 1, wherein the ESCs are cultured in a substrate, optionally wherein the substrate comprises a dish, a U-plate, a flask or a microwell plate (Methods – “Naïve ESC-derived…” p. 3306.e7, 1st para.).
Regarding claim 11, Tarazi teaches the method of claim 1, wherein step (a) comprises culturing the ESCs in a feeder cell (FC) media for about 3 days, and wherein step (a) further comprises culturing the ESCs in an in vitro culture (IVC) media for about 2 days (Results – “sEmbryos self-assembled from naïve…”, p. 3295, 2nd para.) Tarazi’s Aggregation Media (AM) is the equivalent to the instant application’s FC media based on claim 22.
Regarding claim 15, Tarazi teaches the method of claim 11, wherein the FC media and the IVC media comprise a basal culture medium (“Naïve ESC-derived…”, p.3306.e8, 3rd para).
Regarding claim 16, Tarazi teaches The method of claim 15, wherein the basal culture medium comprises (“Naïve ESC-derived…”, p. 3306.e8, 3rd para):
Dulbecco's Modified Eagle Media (DMEM), DMEM Nutrient Mixture 12 (DMEM/F12)
A non-human serum or serum substitute thereof (FBS)
A reducing agent (N-acetyl-L-cysteine)
An antibiotic (Penicillin-streptomycin)
L-glutamine or an analogue thereof (GlutaMAX)
Regarding claim 22, Tarazi teaches the method of claim 11, wherein the FC (AM) media comprises (“Naïve ESC-derived…”, p. 3306.e7, 1st para.):
DMEM
Fetal bovine serum
Sodium pyruvate
GlutaMAX
MEM non-essential amino acids (Sartorius 01-340-1B)
Beta-mercaptoethanol,
IVC media (“Naïve ESC-derived…”, p. 3306.e8, 3rd para.)
ITS-X
Estradiol
N-acetyl-L-cysteine
Progesterone
Penicillin streptomycin
Regarding claim 24, Tarazi teaches the method of claim 11, wherein the FC (AM) media further comprises (“Naïve ESC derived…”, p. 3306.e7, 1st para.):
Heparin
A fibroblast growth factor (FGF4)
ROCK inhibitor (ROCKi Y27632)
Regarding claim 33, Tarazi teaches the method of claim 1, wherein co-culturing the ESCs comprises increasing serum concentrations, optionally increasing the serum concentration from about 20% to about 30%, optionally when the ESCs are co-cultured in the IVC media (“Naïve ESC-derived…” p. 3306.e7, 1st para. (20%) and p. 3306.e8, 3rd para. (30%)).
Regarding claim 35, Tarazi teaches the method of claim 1, wherein step (a) is performed under a static condition and/or wherein step (b) is for a duration of at least 3 days
(Figure S3A).
Regarding claim 37, Tarazi teaches the method of claim 1, wherein the post-implantation culture media is capable of supporting the development of embryo ex utero (“Naïve ESC-derived…”, p. 3306.e8, 5th para.).
Regarding claim 38, Tarazi teaches the method of claim 1, wherein the post-implantation culture media comprises (“Naïve ESC-derived...”, p. 3306.e8, 5th para.):
DMEM
Non-human serum (FBS and Rat)
Human cord serum
L- glutamine or an analogue thereof (GlutaMAX)
Penicillin streptomycin
Regarding claim 40, Tarazi teaches the method of claim 38, wherein the post-implantation culture medium comprises bicarbonate HEPES (“Naïve ESC-derived…”, p. e8, 5th para.).
Regarding claim 43, Tarazi teaches the method of claim 1, wherein the post-implantation culture medium comprises (“Naïve ESC-derived…”, p. 3306.e8, 5th para.):
DMEM,
Rat serum,
Human cord serum,
GlutaMax,
Penicillin and/or streptomycin,
HEPES
Regarding claim 45, Tarazi teaches the method of claim 1, wherein step (b) comprises culturing the gastrulating embryo structure under a dynamic condition in a culture chamber, following culturing the gastrulating embryo structure under a static condition (Figure 2A).
Regarding claim 46, Tarazi teaches the method of claim 45, wherein culturing the gastrulating embryo structure under the static condition is for a duration of about 2 days and/or wherein culturing the gastrulating embryo structure under the dynamic condition is for a duration of at least one day (Figure 2A).
Regarding claim 48, Tarazi teaches the method of claim 45, wherein the dynamic condition comprises suspension agitation, optionally rotation and wherein culturing the gastrulating embryo structure under the dynamic condition is performed in a rotating bottle culture chamber (Figure 2C).
Regarding claim 51, Tarazi teaches the method of claim 1, wherein step (b) comprises supplying the post-implantation culture medium with glucose. (“Naïve ESC-derived…” p. 3306.e8, 5th para.).
Regarding claim 52, Tarazi teaches the method of claim 1, wherein the synthetic embryo structure (1) resembles an E8.0-E8.5 natural embryo structure; (2) is a neutralizing embryo structure; (3) has established headfolds, a beating heart, allantois, chorion structure, and/or yolk sac; and/or (4) has developed amnion-like and yolk-sac-like membranes (Figure 5B and F, p. 3299).
Regarding claim 56, Tarazi teaches the method of claim 1, wherein (1) the method does not comprise any in vivo step; (2) none of the wild-type ESC, the ESC overexpressing CDX2 transcription factor and the ESC overexpressing GATA transcription factor is present in an in vivo environment during step (a) or step (b); and optionally wherein the in vivo environment comprises a tissue, an organ, an organism, or a combination thereof; and/or (3) the method does not comprise culturing an extra-embryonic stem cell, optionally, the extra-embryonic stem cell comprises an extra-embryonic trophoblast stem cell and/or an extra-embryonic endoderm stem cell (Discussion, p. 3302, 2nd and 3rd para.).
Regarding claim 59, Tarazi teaches the method of any one of claim 1,wherein the synthetic embryo is a mouse embryo (Abstract).
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.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Tarazi.
Regarding claim 50, Tarazi teaches all of the elements of the current invention as stated above and provides motivation for optimizing the method of claim 48, wherein the rotating bottle culture chamber contains 30-50 sEmbryos in about 2 ml post-implantation medium (“Naïve ESC-derived…” p. 3306.e8, 4th para.). Tarazi does not teach using 3 synthetic embryoid per rotating bottle culture chamber.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Tarazi’s protocol to find/use the optimal amount of embryoids per chamber for proper growth based on container size, medium volume, etc.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Tarazi, in view of Yao et al. (C.A. Patent Application Publication No. 2843373), hereinafter Yao.
Regarding claim 26, Tarazi teaches all of the elements of the current invention as stated above including the method of claim 11, wherein the IVC media comprises: estradiol and progesterone, but does not teach the use of insulin.
Yao teaches the use of insulin [para. 0034] and insulin-like growth factors (IGF) [para. 0035] for culturing embryos.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified and optimized Tarazi to incorporate the motivation and teachings of Yao to use insulin or analogues thereof for culturing embryos. Doing so would improve embryo quality and implantation potential.
Conclusion
The invention as claimed is anticipated by Tarazi and prima facie obvious over Tarazi, in view of Yao. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached Monday-Friday 9:00A - 5:00P.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638