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 .
DETAILED ACTION
Election/Restriction
Applicant’s election of Group I, claims 1-9 and 13, drawn to a method for constructing a mouse model with short telomere and a method of use of a mouse embryo at blastocyst stage in the production of a mouse model with short telomere, in the reply filed on 08/12/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Status
Claims 1-13 are pending.
Claims 10-12 are withdrawn.
Claims 1-9 and 13 are considered on the merits.
Priority
This application is a 371 of PCT/CN2022/139556 (filed on 12/16/2022), which claims benefit from foreign application CN202211323532X (filed on 10/27/2022). The priority claim of the instant application has been granted and the earliest benefit date is 10/27/2022 from the application CN202211323532X.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/06/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Claim Objections
Claims 1-2, 4-9 and 13 are objected to because of the following informalities:
Claims 1-2, 4-8 and 13 recite multiple limitations and/or steps, however, there is no conjunctions (e.g., “and”, “or”) between these limitations/steps. Thus, the claims may be broadly interpreted as requiring only one of those limitations/steps. It is recommended to add a conjunction to clarify.
Claim 9 recites the phrase “in the tissue of the mouse model” in line 2. It is recommended to change to “in a tissue of the mouse model”.
Furthermore, claim 9 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim (i.e., instant claim 9) cannot depend from any other multiple dependent claim (i.e., instant claim 3). See MPEP § 608.01(n). Accordingly, claim 9 has not been further treated on the merits.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
(Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 and 13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, the limitation “the method does not involve modification of the genetic material of the chromosomes or mitochondria of the mouse, the modification is selected from the group consisting of: gene mutation, gene editing, gene knockout, mutagenesis, and introduction of exogenous nucleic acid” in claim 1 (underlined by examiner) is considered as a negative limitation. M.P.E.P. §2173.05(i) states that any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) (“[the] specification, having described the whole, necessarily described the part remaining.”). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff ’d mem., 738 F.2d 453 (Fed. Cir. 1984). The mere absence of a positive recitation is not basis for an exclusion. Any claim containing a negative limitation which does not have basis in the original disclosure should be rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. Ex parte Parks, 30 USPQ2d 1234, 1236 (Bd. Pat. App. & Inter. 1993). See MPEP § 2163 - § 2163.07(b) for a discussion of the written description requirement of 35 U.S.C. 112, first paragraph.
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 1-9 and 13 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.
Claims 1, 2, 4-6, 9 and 13 recite the term “preferably”, which renders the claims indefinite because it is a subjective term. A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. See MPEP § 2173.05(b). The limitations that are “preferably” are examined as not being required. Claims 3 and 7-8 are rejected as being directly or indirectly dependent from claim 1 but not resolving the ambiguity.
Additionally, claim 1 recites the limitation “the mouse” in line 8. There is insufficient antecedent basis for this limitation because claim 1 recites several mice before this limitation, such as “an embryo at blastocyst stage”, “a surrogate female mouse”, and “a mouse model with short telomere”. Therefore, it is not clear which mouse this limitation is referring to. It is examined as the embryo at blastocyst stage.
Similarly, claim 2 recites “the mouse is SPF grade” in the second last line. There is insufficient antecedent basis for this limitation because many mice are recited, and it is not clear which mouse this limitation is referring to.
Claims 3 and 13 recite the term “NIH(S)”. it is unclear whether the limitation “S” between the parentheses is part of the claimed invention. It is recommended to spell out the term as “NIH Swiss”.
Claim 13 recites “Use of a mouse embryo at blastocyst stage in the production of a mouse model with short telomere”. As stated in the restriction requirement, this claim is interpreted as “a method of use of a mouse embryo at blastocyst stage in the production of a mouse model with short telomere”. MPEP 2173.05(q) states “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: “[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon” was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parteErlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). In the instant case, claim 13 merely recites a use of a mouse embryo in the production of a mouse model, without any active, positive steps delimiting how this use is actually practiced, thus is indefinite.
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.
Claims 1-5, 7-9 and 13 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Itoi et al., (PLoS ONE. 2012; 7(10): e47512, p. 1-9).
With respect to claim 1, it is noted that the limitation “for constructing a mouse model with short telomere" in the preamble and the limitation “to produce a mouse model with short telomere” in claim 1 are interpreted as intended use. MPEP 2111.02 II states “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Thus, the limitations “for constructing a mouse model with short telomere" and “to produce a mouse model with short telomere” do not provide any patentable weight in determining patentability of the claimed method.
Itoi teaches a method of culturing zygotes to blastocysts in vitro and further transferring the blastocysts to pseudopregnant recipients to achieve full-term development (see e.g., abstract, see Fig 1 and Fig 4E for culturing zygotes derived from IVF to blastocysts in vitro and see Fig 4F and Tables 1-3 for offsprings derived from transferring the blastocysts to pseudopregnant recipients). Itoi teaches the zygotes are cultured for 72 hours to reach morula/blastocyst stage (e.g., p. 4, left col., p. 7, right col, section “Embryo Culture on a Warm Plate”, para 2, and see Fig 4E legend) and the morula/blastocyst-stage embryos derived from each culture system are transferred into the uterus of pseudopregnant ICR strain female mice (e.g., p. 4, right col, section “Embryo Transfer”). Thus, Itoi teaches a method comprising the steps of transferring an embryo at blastocyst stage into a surrogate female mouse to produce a mouse model wherein the blastocyst stage refers to 70 to 120 hours after fertilization or 72±2 hours after fertilization. Itoi teaches the mice are female and male B6D2F1 (C57BL/6J x DBA/2) mice and C57BL/6N mice (i.e., wildtype mouse strains, see p. 3, right col, para “Animals”), thus the mouse embryos do not have modification of the genetic material of the chromosomes or mitochondria.
With respect to claim 2, Itoi teaches “Spermatozoa were collected from the cauda epididymidis of B6D2F1 males (>12 weeks) into 200 µl drops of human tubal fluid medium covered with sterile mineral oil and capacitated by incubation for 1-2 h at 37°C under 5% CO2 in air” (p. 3, right col, para “Production of Zygotes from In Vitro Fertilization (IVF)”), thus teaches step 1) obtaining a sperm from a male mouse and contacting the sperm with a capacitation medium to obtain a capacitated sperm.
Itoi teaches “During sperm preincubation, cumulus–oocyte complexes (COCs) were collected from the oviducts of B6D2F1 female mice (8-12 weeks old)” (p. 3, right col, para “Production of Zygotes from IVF”), thus teaches step 2) obtaining a cumulus-oocyte complex from a female mouse and steps 1) and 2) are carried out in parallel.
Itoi teaches “After sperm preincubation, 5 µl aliquots of the suspension were added to droplets of human tubal fluid containing COCs” (p. 3, right col, para “Production of Zygotes from IVF”), thus teaches step 3) contacting the capacitated sperm with the cumulus-oocyte complex in vitro to obtain a fertilized egg.
Itoi teaches the zygotes are cultured in different culture systems and “The rates of development to 2-cell embryos or to the morula or blastocyst stage at 72 h were calculated from all the zygotes collected” (p. 4, left col), thus teaches step 4) allowing the fertilized egg (i.e., zygotes) to develop to the blastocyst stage in vitro.
Itoi teaches “Morula/blastocyst-stage embryos derived from each culture system were transferred into the uterus of pseudopregnant ICR strain female mice” (p. 4, right col, section “Embryo Transfer”), thus teaches step 5) transferring the embryo at blastocyst stage into a surrogate female mouse.
Itoi teaches “Offspring were obtained at 18.5 days post copulation through Cesarean section or by natural birth” (p. 4, right col, section “Embryo Transfer”), thus teaches step 6) delivering the mouse model from the surrogate female mouse.
With respect to claim 3, as stated supra, Itoi teaches the mice are strains of B6D2F1 (C57BL/6J x DBA/2) mice and ICR strain female mice (see p. 3, right col, para “Animals” and p. 4, right col, section “Embryo Transfer”).
With respect to claim 4, as stated supra, there is no conjunction recited in the claim thus the claim is broadly interpreted as only requiring one limitation. Itoi teaches sperm is collected from male mouse (>12 weeks) and cumulus–oocyte complex is collected from female mouse (8-12 weeks old) (within the claimed ranges, see p. 3, right col, para “Production of Zygotes from IVF”).
With respect to claim 5, as stated supra, Itoi teaches “Spermatozoa were collected … into 200 µl drops of human tubal fluid medium covered with sterile mineral oil and capacitated by incubation for 1-2 h at 37°C under 5% CO2 in air” (p. 3, right col, para “Production of Zygotes from IVF”).
With respect to claims 7 and 8, Itoi teaches “some embryos of the B6D2F1 strain were cultured on a warming plate at 37°C after being sealed in a plastic bag following the deoxidizing treatment and covered with aluminum foil (DeO2-WP experiment)”, and teaches “To determine the effect of the deoxidizing agent, the air in the plastic bag was aspirated and replaced with a gas mixture (5% CO2, 5% O2 and 90% N2)” (p. 4, left col). Itoi teaches the embryos are cultured for 48 hours to reach 8-cell-stage (see Fig 4D legend) and are cultured for 72 hours to reach morulae/blastocysts on the warm plate (see Fig 4E legend). Thus, Itoi teaches the fertilized egg is contacted with a medium (i.e., a cleavage medium) at 37°C with 5% CO2 for 48 hours to obtain an embryo at 8-cell stage and the embryo at 8-cell stage is contacted with a culture medium (i.e., a blastocyst culture medium) at 37°C with 5% CO2 for additional 24 hours (i.e., a total of 72 hours) to obtain an embryo at blastocyst stage in claims 7 and 8.
With respect to claim 9 directed to the telomere length in the tissue of the mouse model is statistically significantly shorter than that of a control mice of the same strain, it must be noted that these wherein clauses do not recite an active step in the claimed method, but only the results of the transferring step as taught by Itoi. MPEP 2111.04 (I) states a whereby clause (or a wherein clause) “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, these wherein clauses do not provide any patentable weight in determining patentability of the claimed method. Claim 9 is rejected in the same way as base claim 1 as discussed above.
With respect to claim 13, similarly as discussed above, the limitation of “production of a mouse model with short telomere” is interpreted as intended use and thus does not provide any patentable weight in determining patentability of the claimed method. See MPEP 2111.02 II. As stated supra, Itoi teaches a method of culturing zygotes to blastocysts for 72 hours in vitro and further transferring the mouse embryos at blastocyst stage to pseudopregnant recipients to produce offsprings (see e.g., abstract, see Fig 4E legend for 72 hours culturing and Fig 4F & Tables 1-3 for offsprings produced, i.e., the claimed mouse model). Thus, Itoi teaches a method of use of a mouse embryo at blastocyst stage in the production of a mouse model wherein the blastocyst stage refers to 70 to 120 hours after fertilization.
Accordingly, Itoi anticipates instant claims.
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.
Claims 1-9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Itoi et al., (PLoS ONE. 2012; 7(10): e47512, p. 1-9) in view of Kidder (Methods Mol Biol. 2014; 1150: 191-199).
Claims 1-5, 7-9 and 13 are anticipated by Itoi, thus are made obvious by Itoi.
With respect to claim 6, as stated supra, Itoi teaches the sperm is capacitated in drops of human tubal fluid medium (“HTF medium”) at 37°C under 5% CO2 in air, and after sperm preincubation, the capacitated sperm is added to droplets of HTF medium (i.e., an in vitro fertilization medium) containing the cumulus-oocyte complex (COCs) for in vitro fertilization for 1.5 hours (p. 3, right col, para “Production of Zygotes from IVF”). One of ordinary skill in the art would have immediately expected that the capacitated sperm would have been contacted with the cumulus-oocyte complex in an in vitro fertilization medium under the same incubation condition as that of sperm capacitation, i.e., at 37°C under 5% CO2 in air.
However, Itoi teaches contacting the capacitated sperm and the cumulus-oocyte complex (COCs) in the HTF medium for 1.5 hours, but is silent on for 4 to 10 hours.
Kidder describes protocols for in vitro fertilization (IVF) of mouse oocytes and preimplantation embryo culture and teaches the protocols are suitable for the study of oocyte and embryo biology and the production of embryonic mice (e.g., abstract). Kidder teaches “Add 10 μL sperm to the COCs in the drop of HTF media, and incubate at 37 °C with 5% CO2 for 4-6 h” (p. 197, section 3.6 “IVF of mouse oocytes”, step 5).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for in vitro fertilization by contacting the capacitated sperm and the COCs in the HTF medium for 1.5 hours disclosed by Itoi, by substituting the 1.5 hours with 4-6 hours as suggested by Kidder with a reasonable expectation of success. Since Kidder reduces to practice a 4-6 hour-incubation to fertilize the oocytes and teaches the protocols are suitable for the production of embryonic mice (see above), one of ordinary skill in the art would have had a reason to substitute 4-6 hour-incubation for the 1.5 hour-incubation of Itoi in order to ensure oocytes to be fertilized to produce embryonic mice.
Furthermore, because Kidder teaches the incubation time is a results effective variable (see e.g., “After 4 h of incubation, the oocytes should be fertilized”, p. 197, section 3.6, step 6), it would have been obvious to one having ordinary skill in the art at the time the invention was filed to apply the claimed incubation time, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANJIAN ZHU/Examiner, Art Unit 1631
