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 .
Applicant’s amendment and response filed on 6/10/2026 has been received and entered into the case.
Claims 7-8 and 13 have been canceled, claims 12, 14-21 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-6 and 9-11 have been considered on the merits. All arguments have been considered.
Response to Amendment
The claim rejections under 35 USC 112 have been withdrawn due to the instant amendment. It is noted that a new 112(a) written description rejection is presented based on the instant amendment.
Claim Objections
Claims 1 and 3-4 are objected to because of the following informalities: the newly amended portion of the claims contains extra space between words. Applicant is advised to format the words in the claims using a proper alignment. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6 and 9-11 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.
Claim 1 discloses that the claimed method would produce totipotent stem cells. The claimed method utilizes one of the listed species and any one of the claimed environmental pressure would sufficiently and necessarily produce totipotent stem cells from any somatic cells. The instant specification provides the definition to the term “totipotent” referring to a cell that has the potential to develop into any cell found in a body, such as a body of a mammal.
First, there is no sufficient written description how to determine the engineered cells are totipotent. The instant specification discloses that Epinul cells are positive for nuclear Oct-4, Oct-4A, Nanog, Sox-2, and TERT detected by RT-PCR and immunostaining (para. [0100]), and these markers are known to be pluripotent stem cell
or embryonic stem cell markers (see Kim at para. [0140]).
Second, the specification did not provide any one of the claimed environmental pressure would produce the claimed totipotent stem cells. The specification discloses Example 1 for the production of synthetic engineered totipotent cells, however, the example does not particularly disclose that any single environmental pressure was sufficient enough to produce the claimed totipotent stem cells from somatic cells. Rather, paragraph [0280] discloses “Directed applications of electromechanical, electromagnetic, frequency shifting and ablation, extreme heat through cavitation and environmental factors associated with excitation of specific genes; and enhancement of this catalyst through engineered and specifically timed alterations to environment, drive the genome of somatic cells to full pluripotency.”
The specification discloses that the claimed cells, i.e. Epinul cells, are produced by Janus Protocol, however, the specification does not particularly show each of the listed environmental pressure individually is capable of producing the claimed cells, or the combination of the several pressures is required. Paragraph [0100] merely states that Epinul cells are produced by mechanistic, chemical and/or electromagnetic means, and yet paragraph [0114] states that a specific sequence of temperature shock and mechanical force is applied to the cells, comprising partial protease digestion, cold shock, ultrasound and pipetting; heat shock, cold shock. There is no disclosure and working example supporting each individual pressure is sufficient for the claimed method or the specific order of the combined pressures is required.
While it is known in the art that totipotent stem cells can be dedifferentiated from somatic cells according to Vacanti et al. (of record), however, the instant specification failed to provide sufficient written description such that any individual environmental pressure as claimed would produce the claimed cells.
It is also noted that the claims disclose that trituration with a pipette having a bore size larger than the cells can sufficiently produce the totipotent stem cells from somatic cells. It is extremely well known in the art that any mammalian cell culture involves passaging the cells using a pipette tip larger than cell size (e.g. 1 ml pipette tip or Pasteur pipette) to dissociate the cell pellet after trypsinization and centrifugation. This process involves the cells in suspension in a medium. The instant claims allege that such a routine experimental procedure would change the fate of any somatic cells to totipotent stem cells. There is no such evidence available in the art as well as in the instant specification. While combined treatment with a specific order might be able to produce totipotent stem cells from any somatic cells, however, there is no sufficient written description that any single treatment of the claimed species (sonication/ultrasound; trituration or heat shock) is sufficient to produce totipotent stem cells.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” and further, “The description needed to satisfy the requirements of 35 U.S.C. 112 "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.< Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art. In most technologies which are mature, and wherein the knowledge and level of skill in the art is high, a written description question should not be raised for claims >present in the application when originally filed,< even if the specification discloses only a method of making the invention and the function of the invention. See, e.g., In re Hayes Microcomputer Products, Inc. Patent Litigation, 982 F.2d 1527, 1534-35, 25 USPQ2d 1241, 1246 (Fed. Cir. 1992) ("One skilled in the art would know how to program a microprocessor to perform the necessary steps described in the specification. Thus, an inventor is not required to describe every detail of his invention. An applicant's disclosure obligation varies according to the art to which the invention pertains. Disclosing a microprocessor capable of performing certain functions is sufficient to satisfy the requirement of section 112, first paragraph, when one skilled in the relevant art would understand what is intended and know how to carry it out."). In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1-6 and 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim (WO 2016/089178, IDS ref.; English translation is relied on US 2017/0327814, supra) in view of Vacanti et al. (supra) in further view of Chatterjee et al. (2016, Methods Mol Biol.; IDS ref.) and as evidenced by Bionumbers (2026, downloaded from https://bionumbers.hms.harvard.edu/bionumber.aspx?s=n&v=3&id=100432).
Kim teaches a method of producing pluripotent cells by applying energy such as ultrasonic waves to differentiated cells (i.e. somatic cells) including human dermal fibroblast cells (see abstract; para. [0100]).
Kim teaches that a cell culture medium and differentiated cells are mixed and energy is applied to the resulting mixture (para. [0085]), and these teachings meet the step of suspending the cells in a medium and exposing the cell suspension to environmental pressures.
Regarding the step of subjecting a population of somatic cells to a partial protease digestion (claim 1), Kim do not particularly teach the limitation.
However, it is extremely well known in the art that the differentiated cells utilized in Kim’s method (i.e. human dermal fibroblasts) are typically grown as an adherent culture (monolayer culture), and the fibroblasts need to be harvested in order to carry out the steps taught by Kim. As Kim teach that the method utilize a suspension culture to form spheroids (para. 118), one skilled in the art would recognize that the fibroblasts would be treated with a protease/proteinase (e.g. trypsin) for dissociation and a suspension culture. Thus, it would have been obvious to a person skilled in the art to treat the human dermal fibroblasts of Kim with a proteinase (e.g. trypsin) to partially digest and release the cells from the culture plate prior to mix the cells with the cell culture medium (i.e. human ES cell medium; see Fig. 1; para. [0121]) for suspension culture to form spheroids. The term “suspension medium” is interpreted as any medium to maintain the cells in suspension. As Kim teaches a suspension culture to which the energy is applied (para. 98), it is considered that the medium of Kim utilized for a suspension culture would meet the limitation.
Regarding the step of subjecting the cell suspension to the environmental pressures selected from (i) acoustic energy; (ii) mechanical stress; or (iii) thermal stress, Kim teaches the ultrasonic waves treatment and thus, it meets the limitation.
Regarding the acoustic energy comprising applying ultrasound to the cell suspension for 10-30 seconds with a pulse repetition frequency 100 Hz – 20 kHz, Kim teaches that the ultrasound treatment of the culture medium may be performed by treating the culture medium with ultrasound having an output intensity of 1 W/cm2 to 20
W/cm2 for 1 to 20 minutes, specifically, with ultrasound having an output intensity of 2 W/cm2 to 10 W/cm2 for 5 to 15 minutes, more specifically, with ultrasound having an output intensity of 3 W/cm2 to 7 W/cm2 for 7 to 13 minutes (para. 88). Kim also teaches that known ultrasound generation devices that generate ultrasound having a frequency of 10 kHz to 100 MHz may be used as the ultrasound generation device without limitation (para. 111).
While Kim does not particularly teach the claimed duration of 10-30 seconds, however, one skilled in the art would recognize that the duration of ultrasound treatment of Kim can be readily modifiable to obtain the desired outcome of the method of dedifferentiating somatic cells into totipotent stem cells. Furthermore, the duration taught by Kim includes 1 min. which is close enough to the claimed range. MPEP2144.05(I) states “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
Regarding the step of transferring the cells to a growth medium to generate totipotent stem cells, Kim teach that the viable cells after the ultrasound stimulation were selected and cultured for 6 days in human ES cell culture medium (para. [0121]), and this step is considered to meet the limitation.
Regarding the acoustic energy, mechanical stress and thermal stress (claim 2), Kim does not particularly teach the limitation.
Vacanti et al. teach a method of reprogramming somatic cells to pluripotent stem cells by using environmental stimuli including ultrasonic stimulation (para. [0005], [0006], [0084]), and the environmental stimuli include any unphysiological stress in tissue or cell culture such as mechanical stimuli, chemical exposure, ultrasonic stimulation, exposure to extreme temperatures, dissociation, trituration, physical stress, etc. and multiple environmental stimuli can be applied to a cell concurrently or separately (para. [0084]). Vacanti et al. teach that the reprogrammed cells can be a totipotent cell (para. 162; p.52, claim 90).
It would have been obvious to a person skilled in the art to use multiple environmental stimuli including ultrasonic stimulation and trituration/dissociation (i.e. pipetting; mechanical stress), and extreme temperature (i.e. thermal stress) for the method of Kim based on the teaching of Vacanti et al. with a reasonable expectation of success.
Regarding the mechanical stress limited to pipetting 3-20 time through a pipette comprising a bore larger than the cells required by claims 2-4, while Kim in view of Vacanti et al. teach trituration, however, they do not particularly teach the number of pipetting as claimed. However, it would have been obvious to a person skilled in the art to adjust the number of pipetting to apply the mechanical stress sufficient to produce the desired outcome in reprogramming somatic cells into totipotent stem cells. It is noted that Vacanti et al. teach trituration using a Pasteur pipette having an internal diameter of 50 mm (para. 88), and this size would meet the bore size larger than the diameter of the cells considering the average diameter of fibroblast in suspension (which would be round shape rather than spindle shape) being about 10-20 mm (see Bionumbers) although they teach the aperture smaller than the size of the cell.
Regarding the thermal stress comprising heat shocking at a temperature between 60 and 80°C for between 50 seconds and 5 min required by claims 2-4, while Kim teaches heat treatment however it does not teach the claimed temperature and the duration. Vacanti et al. teach exposure to extreme temperature for the reprogramming somatic cells into totipotent cells, and the temperature can be above 42°C including a temperature of about 85°C or higher (para. 96), and thus, the claimed range overlaps with the teaching of Vacanti et al. Regarding the duration/length, Vacanti et al. teach the length of extreme temperature exposure being longer than the claimed range. However, Vacanti et al. teach that clearly the higher the temperature, the shorter the exposure, and thus, it would have been obvious to a person skilled in the art to adjust the length of the temperature treatment in order to obtain the desired outcome of the method taught by Kim in view of Vacanti et al. with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because the duration/length of treatment is considered as a result-effective parameter that can be readily modified by routine experimentations.
Regarding claims 3-4 directed to the order of individual environmental pressures, Kim in view of Vacanti et al. do not particularly teach the limitations. However, in the absence of any evidence to the contrary, it is considered that the steps of applying environmental pressures/stresses can be in any order. M.P.E.P. § 2144 recites, “The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law…If the facts in a prior legal decision are sufficiently similar to those in an application under examination, the examiner may use the rationale used by the court.” In In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), the court found that selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930), the court found that selection of any order of mixing ingredients is prima facie obvious.
Regarding claims 5-6 directed to the somatic cells comprising mammalian cells including human cells, Kim teaches human dermal fibroblasts (HDFs) for the method.
Regarding the presence of ATP in a culture medium for the step of applying environmental pressure (claim 9), Kim do not teach the limitation.
Vacanti et al. teach the use of ATP to induce the generation of pluripotent cells (para. [0091]).
It would have been obvious to a person skilled in the art to use ATP as taught by Vacanti et al. for the method of Kim with a reasonable expectation of success since ATP is useful in the method of producing pluripotent stem cells from somatic cells using environmental stimuli as taught by Vacanti et al.
Regarding the culture medium with LIF (claim 10), Kim do not teach the limitation. However, it is known in the art that induced pluripotent stem cells derived from somatic cells (iPSCs) are cultured in high glucose DMEM, and recombinant Leukemia Inhibitory Factor (LIF) according to Chatterjee et al. (see p.4, 2.3. Medium and Growth factors; (m) iPS cell complete medium). Thus, it would have been obvious to a person skilled in the art to use high glucose for the ES cell culture medium of Kim with a reasonable expectation of success.
Regarding claim 11 directed to the step of treating the cell suspension with proteinase K after subjecting the cell suspension to the environmental pressure and before transferring the cells to the growth medium, Kim teach that DNA was extracted from the Physics spheroids (i.e. cell suspension after ultrasonic stimuli) by using proteinase K and the methylation of OCT3/4 and NANOG DNAs in the Physics spheroid was analyzed (para. 146). This teaching would meet the limitation of claim 11.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 6/10/2026 have been fully considered but they are not persuasive. First, the claim rejection under 35 U.S.C. 103 has been modified to address the newly added limitations.
Applicant argued that a person skilled in the art would not look to combine Kim and Vacanti because they employ conditions that are physically incompatible with each other. Applicant compared the teaching of Kim and Vacanti for the different treatment conditions, and alleged that the teachings of Kim and Vacanti are not identical in the ranges of the parameters, and there is no reason to modify the teachings of Kim and Vacanti to arrive the claimed method.
The Examiner respectfully disagrees with this argument. As discussed in the claim rejection above, the parameters for the claimed environmental pressure/stress as claimed are result-effective and thus, one skilled in the art would readily adjust to obtain the desired outcome. As Kim and Vacanti teach various environmental pressure/stress as claimed, the specific parameters and conditions for the environmental pressure/stress would be optimized by routine experimentation, and by doing so, one skilled in the art would arrive to the claimed parameters for the environmental pressure.
Thus, in the absence of the criticality of the claimed parameters and/or unexpected results produced by the claimed method, and the combined teachings of Kim and Vacanti recognize that the environmental pressure/stress would reprogram the somatic cells into totipotent stem cells, it is the Examiner’s position that the cited references render the claimed invention obvious.
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 TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES SCHULTZ can be reached at 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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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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