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 28-47, filed on Nov. 21, 2025, are pending and examined below.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has complied with the conditions for receiving the benefit of an earlier filing date; as such, the earliest priority date of this application is Dec. 19, 2017.
Information Disclosure Statement
The information disclosure statement filed Jan. 2, 2024 is incompliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
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 28-47 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.
Applicants have not adequately shown that they had possession of the invention claimed as it is noted that the only requirement of the claims is that the gas pressure level in an incubator be regulated to a set pressure level of 14.69 – 18 psi, and that this parameter provides a method of modulating a potency-level phenotype of at least a subset population of cells, as exposure to the set pressure level causes the altered potency-level phenotype.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would leave one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP 2163.
A claimed genus may be satisfied through sufficient descriptions of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with known or disclosed correlation between function and structure. MPEP 2163(3)a(II). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
(a) actual reduction to practice
The applicants have demonstrated no actual reduction to practice of the broadly claimed modulating a potency-level phenotypes by regulating a total gas pressure in an incubator to 14.69 – 18 psi and thereby altering the potency-level phenotype (claim 28), modulating expression of differentiation (claim 29) or modulation of cell mophorology or other cell properties (claim 30).
The specification discloses that specific combination of oxygen level and increased gas pressure (2 psi, presumably 2 psi above atmospheric pressure) for specific times give specific results. For example, hematopoietic stem cell differentiation can be regulated during culture by exposure to 3% O2 and 2 PSI (again, presumably 2 PSI above the standard PSI of 14.7) for the first 6 days, followed by incubation of 15% O2 and 2 PSI for 8 days. (para. [0138]) Notably, there are no examples of reduction to practice where cells were exposed only to a set pressure level of 14.69-18 psi. Rather, cells are different cells were cultured under specific parameters (with specific O2 and gas pressure levels) for specific time periods. Throughout the disclosure, the pressures are indicated as only 0 psi (presumably no increase over atmospheric pressure) and 2 psi (presumably, increased 2 psi beyond atmospheric pressure; that is approximately 16.7 psi.). There is no support for a range of 14.69 – 18 psi, rather there is support for culturing, under specific O2 parameters for specific time periods, using either atmospheric pressure or increasing the atmospheric pressure by 2 psi (16.7 psi).
(b) disclosure of drawings or structural chemical formulas
The drawings do not provide support for a method of modulating a potency-level phenotype of a population of cells by only regulating a total gas pressure in an incubator. Fig. 1a depicts both oxygen level and psi over ambient as factors that affect phenotype. Fig. 2 indicates that pressure level, oxygen level, induction factors and trophic factors during culturing all play a role in regulating phenotype. Fig. 3A indicates that human fibroblasts cultured in specific oxygen levels and pressure levels with factors become iPSCs which can be further cultured in mTesr1 at 0 and 2 PSI. Fig. 3C-3F further supports the idea that both oxygen level and pressure level being different than ambient may cause changes in phenotype.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure
The applicants do not have any complete or partial properties that would enable one of ordinary skill in the art to determine how to use only a set pressure level of an incubator to modulate the potency level of the phenotype of a subset population of cells.
(d) representative number of samples.
Applicants have not provided a representative number of samples. Every time a specific cell modulation of phenotype is discussed, there is a specific oxygen level, a specific pressure and it is acknowledged that other factors (such as transcription factors, cytokines, or growth factors) are necessary. (para. [0011]) There is nowhere in the present disclosure where changing a cell’s phenotype is discussed as being only dependent on the total gas pressure of an incubator the cells are present in. There is no discussion of a pressure level of 14.69 – 18 psi. There is discussion of atmospheric pressure – 0 psi (14.69 psi) and 2 psi (16.69 psi) and only in conjunction with reduced oxygen pressure.
Claims 28-47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for culturing of specific cell types in specific oxygen and pressure conditions with specific bioactive factors present for specific time periods, does not reasonably provide enablement for gas pressure level in an incubator be regulated to a set pressure level of 14.69 – 18 psi, and that this parameter provides a method of modulating a potency-level phenotype of at least a subset population of cells, as exposure to the set pressure level causes the altered potency-level phenotype. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach
those skilled in the art how to make and use the full scope of the claimed
invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561
(Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the
Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of
experimentation is permissible, if it is merely routine, or if the
specification in question provides a reasonable amount of guidance
with respect to the direction in which experimentation should
proceed to enable the determination of how to practice a desired
embodiment of the claimed invention.
PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
1As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1) the nature of the invention,
2) the breadth of the claims,
3) the state of the prior art,
4) the predictability or unpredictability of the art,
5) the relative skill of those in the art,
6) the amount of direction or guidance provided,
7) the presence or absence of working examples,
8) the quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833,839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1) The nature of the invention and 2) the breadth of the claims
The claims are drawn to a method of regulating a gas pressure level in an incubator to a set pressure level of 14.69 – 18 psi, and that this parameter provides a method of modulating a potency-level phenotype of at least a subset population of cells, as exposure to the set pressure level causes the altered potency-level phenotype. Thus, the claims taken together with the specification imply that Applicant is claiming that only regulation of the pressure level of an incubator in a range of 14.69 psi (atmospheric pressure) – 18 psi will work to modulate phenotype of at least a subset cell population.
3) the state of the art, 4) unpredictability of the art and 5) the relative skill
of those in the art
The relative skill of those in the art is high, generally that of a PhD in biochemistry or cell biology or a research physician.
That factor is outweighed however by the unpredictable nature of the art.
As disclosed by applicants, the specific combination of oxygen level and increased gas pressure (2 psi, presumably 2 psi above atmospheric pressure) for specific times give specific results. For example, hematopoietic stem cell differentiation can be regulated during culture by exposure to 3% O2 and 2 PSI (again, presumably 2 PSI above the standard PSI of 14.7) for the first 6 days, followed by incubation of 15% O2 and 2 PSI for 8 days. (para. [0138]) Notably, there are no examples of reduction to practice where cells were exposed only to a set pressure level of 14.69-18 psi. Rather, cells are different cells were cultured under specific parameters (with specific O2 and gas pressure levels) for specific time periods. Throughout the disclosure, the pressures are indicated as only 0 psi and 2 psi (approximately 16.7 psi.). Furhtermore, the specification acknowledges that other factors (such as transcription factors, cytokines, or growth factors) are necessary. (para. [0011]).
As Tworkoski et al. (PLoS ONE, 2018) explains, a number of studies have reported changes in cell behavior following the application of 10 -150 mmHg changes in hydrostatic pressure (an increase of 103.43 mmHg = 2 psi) during cell culture, including cell proliferation, migration, apoptosis, cell morphology, and gene expression. (Introduction) Tworski et al. replicated previously conducted studies to determine if the rate of the pressure change could account for the changes to cells. (Introduction). Tworkoski et al. could not confirm many of the reported changes from the literature. (Table 1, Discussion). Tworkoski et al. further teach that other groups have failed to reproduce altered cell behavior through increased hydrostatic pressure. (Discussion). Tworkoski et al. conclude, “Our study joins a growing body of literature questions whether moderate levels of hydrostatic pressure elevation have any effect on living cells. Nonetheless, there are a large number of studies that reported such effects; our results do not explain their findings.” As such, the art generally requires a specific cell type, being cultured under specific conditions, using specific bioactive factors to accept results as valid.
6) the amount of direction and guidance provided and 7) the presence and absence of working examples
As explained above in the written description rejection, (see supra), the specification does not provide enough direction and guidance, nor any working examples, where pressure alone within the claimed range results in modulation of cell phenotype.
Because of the absence of working examples and guidance and the general recognition in the art that experiments using pressure modulation only are often not replicable, there is no reasonable expectation that regulating a gas pressure level in an incubator to a set pressure level of 14.69 – 18 psi will modulate a potency-level phenotype of at least a subset population of cells.
8) The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and
in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept the assertion that regulating a gas pressure level in an incubator to a set pressure level of 14.69 – 18 psi will modulate a potency-level phenotype of at least a subset population of cells as inferred in the claims.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable." (42 USPQ 2d 1001, Fed. Circuit 1997).
To practice the invention of the instant claims required undue experimentation due to unpredictability in culturing cells under variable pressure. As Tworkoski et al. explains, “Our study joins a growing body of literature questions whether moderate levels of hydrostatic pressure elevation have any effect on living cells. Nonetheless, there are a large number of studies that reported such effects; our results do not explain their findings.”
To practice the invention of the instant claims requires undue experimentation due to the unpredictability of cell behavior when exposed to varying gas pressure levels, and the lack of direction from Applicants regarding the same. The amount of experimentation required in order to regulate a gas pressure level in an incubator to a set pressure level of 14.69 – 18 psi to modulate a potency-level phenotype of at least a subset population of cells is extremely large due to other factors which influence cell culture (oxygen level, bioactive factors, time periods) and the unlikelihood that gas pressure changes alone are response for changes in cell behavior. To determine if regulating a gas pressure level in an incubator to a set pressure level of 14.69 – 18 psi will modulate a potency-level phenotype of at least a subset population of cells would require inventive effort and extensive experimental burden.
In light of the above discussion, the claims do not comply with the enablement requirement of 35 U.S.C. § 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634