DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 5 May 2026. Claims 14 and 28 have been amended. Claims 21-24 remain withdrawn. Claims 14-20 and 25-32 are currently pending and under examination.
This Application is a Continuation of U.S. Application No. 15/531532, filed May 30, 2017, now U.S. Patent No. 10,744,160, which is a national phase application under 35 U.S.C. §371 of International Application No. PCT/RU2015/000831, filed November 30, 2015, and claims priority to Russian Patent Document No. RU2014148251, filed December 1, 2014.
Withdrawal of Objections/Rejections:
The objection to claims 18, 31, and 32 as being dependent upon a rejected base claim, but would be allowable if rewritten in independent, is withdrawn.
The rejection of claims 14-16, 20, 25 and 27-29 under 35 U.S.C. 103 as being unpatentable over Gordon-Beresford et al., is withdrawn.
The rejection of claims 14, 17, and 30 under 35 U.S.C. 103 as being unpatentable over Gordon-Beresford et al., and further in view of Lee et al., is withdrawn.
The rejection of claims 14, 19, and 26 under 35 U.S.C. 103 as being unpatentable over Gordon-Beresford et al., and further in view of Brem et al., is withdrawn.
New Rejections Necessitated by Amendment:
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 14-20 and 25-32 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In In re Wands (858 F2d, 731, 737, 8 USPQ 2d 1400, 1404 (Fed Cir. 1988)) the issue of enablement in molecular biology was considered. It was held that the following factors should be considered to determine whether the claimed invention would require of the skilled artisan undue experimentation:
1) Quantity of experimentation necessary;
2) Amount of direction or guidance presented;
3) Presence or absence of working examples;
4) Nature of the invention;
5) State of the prior art;
6) Relative skill of those in the art;
7) Predictability or unpredictability of the art; and
8) Breadth of the claims.
For all of these reasons, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention.
Quantity of experimentation necessary; 2) Amount of direction or guidance
presented; 3) Presence or absence of working examples: Regarding independent claims 14 and 28, the specification provides guidance for the single cell line “hb-MSC”-produced conditioned media (hb-MSC was deposited with VKPM accession number H-154 and deposited under the name MSCR05P09; see Specification, para. 18), examples that show the effectiveness of hb-MSC conditioned medium for reducing wound size (Fig. 4, 5), and that other single cell line conditioned media, such as rb-MSC conditioned media, does not provide the same in vivo results (see Fig. 4-7). The specification specifically teaches:
[34] The hb-MSC line differs significantly from other lines of stem cells obtained from rats, as can be illustrated using a number of different characterization methods. Rat mesenchymal stem cells obtained under standard conditions were cultured to show the differences between the typical rat mesenchymal stem cell and the unique hb-MSC line. The typical rat mesenchymal cell line prepared for purposes of this comparison was termed the rb-MSC line. To obtain the rb-MSC line, pl rat mesenchymal cells were passaged according to standard conditions known in the art, as described in Example 2.
Further, the Specification (Table 3, reproduced below) indicates that only conditioned media of hb-MSC is capable of providing the factors in the amounts as claimed:
TABLE 3 – Comparison of factor concentration for rb-MSCs and hb-MSCs in pg/ml
Factor
rb-MSC
hb-MSC
IL-10
0 to 12
12 to 38
IP-10
7 to 26
18 to 120
GRO/KC
14 to 100
460 to 5600
VEGF
300 to 2400
760 to 15800
OPG
540 to 3200
0 to 90
TGF-β1
550 to 2600
67 to 2000
TGF-β2
520 to 3200
170 to 2900
TGF-β3
100 to 610
0 to 40
Additionally, there are additional components necessary to provide the claimed conditioned media with at least 4,000 pg/ml of VEGF, as well as at least 750 pg/ml of TGF-β1 and at least 250 pg/ml TGF-β2, even when the hb-MSC cell line is utilized that are not provided. Applicant indicates, referring to the data in Table 3, which includes the hb-MSCs:
[82] The range of factors observed during the analyzed time periods is summarized in Table 3 below. It should be understood that concentration of factors may depend on the time period that the cells are cultured and number of cells in the flask (emphasis added).
It is clear that the only cell line listed in the specification capable of providing the conditioned media as claimed is hb-MSC. Further, it is clear that additional elements that account for the VEGF being at least 4,000 pg/ml (instead of only 750-3,999 pg/ml) as well as the TGF-β1 being at least 750 pg/ml (instead of only 67-749 pg/ml) and TGF-β2 being at least 250 pg/ml (instead of only 170-249), are required to be present, as this cell line is shown to produce well under the claimed amounts (see Table 3). Further, the only guidance and direction presented for other single cell lines include rb-MSC. However, this cell line is not capable of providing conditioned media with VEGF being at least 4000 pg/ml as claimed (see Table 3). The quantity of experimentation necessary to determine the conditioned media as claimed, without the cell line required to produce it, or any components/conditions of production, is very high.
4) Nature of the invention; 5) State of the prior art: The invention is complex, and while there is guidance regarding conditioned media, guidance regarding conditioned media from a single cell line that includes the factors as claimed, absent a cell type and other culture conditions, is uncertain.
6) Relative skill of those in the art: Those working in this art are highly skilled.
7) Predictability or unpredictability of the art: As evidenced by the instant Specification, the art is complex and highly unpredictable, as single cell lines from the same origin (bone marrow of Wistar rats) produce conditioned media with different factors/concentrations, as seen with hb-MSC conditioned medium vs. rb-MSC conditioned media (see Table 3; Para. 34, 70).
8) Breadth of the claims: The claims are extremely broad and encompass conditioned medium from any single cell line, including those not found to be effective to produce the mixture of factors recited in the claims, and therefore are not enabled.
Claims 14-20, 25-27, and 29-32 are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
Claims 14-20 and 25-32 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 claims 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.
Claims 14 and 28 recite a “conditioned media of a single cell line.” These claims and those depending therefrom are considered genus claims that encompass a wide array of single cell lines that provide conditioned media. The specification fails to set forth a representative number of examples in order to reasonably verify possession of such a potentially enormous number of single cell line-conditioned media.
The MPEP states that written description for a genus can be achieved by a representative
number of species within a broad generic. It is unquestionable that the claims are broad generics,
with respect to all conditioned media of single cell lines.
The purpose of the written description requirement is to ensure that the inventor had
possession, as of the filing date of the application, of the specific subject matter later claimed. A patent specification must describe an invention and do so in sufficient detail, so that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention with all of its limitations,” and by using "such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention" (see MPEP 2163).
Here, the specification lacks a sufficient variety of species of single cell lines that provide the conditioned media, to reflect this variance in the genus in the composition for in vivo application comprising the claimed factors. Accordingly, the specification fails to provide adequate written description for the genus of "conditioned media of a single cell line" and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention. Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent such teachings and guidance as to the structure and function of these single cell lines that provide the conditioned media in the composition for in vivo administration, the specification does not describe the claimed conditioned media of a single cell line in such full, clear, concise and exact terms so as to indicate that applicant had possession at the time of filing of the present application. Thus, the written description requirement has not been satisfied.
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 14-20 and 25-32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the single cell line “hb-MSC” that produces the claimed conditioned media, and the additional components responsible for providing the factors (VEGF, TGF-β1, TGF-β2) in the claimed amounts.
Regarding independent claims 14 and 28, the specification shows that the single cell line necessary for producing the conditioned media as claimed is hb-MSC. It is shown in the specification that other conditioned media from single cell lines, such as rb-MSC conditioned media, do not provide the same in vivo results or contain the same components (see Fig. 4-7; Table 3). As can be seen in Table 3 of the instant Specification (reproduced previously), only conditioned media of hb-MSC is capable of providing the factors in the amounts as claimed.
Additionally, even when the hb-MSC cell line is utilized, there are components necessary to provide the claimed composition that are missing from the claims. It is clear that additional elements/conditions are required to be present to account for the VEGF being at least 4000 pg/ml (instead of only 750-3999 pg/ml), as well as the TGF-β1 being at least 750 pg/ml (instead of only 67-749 pg/ml) and TGF-β2 being at least 250 pg/ml (instead of only 170-249), as even hb-MSC is shown to produce amounts outside of the claimed ranges (see Table 3). It is indicated in the specification that the concentration of factors in the conditioned media may depend on the time period that the cells are cultured and number of cells in the flask (Para. 82).
For the forgoing reasons, these claims are deemed to be missing essential features.
Claims 14-20, 25-27, and 29-32 are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
Response to Arguments
In view of Applicant’s amendments, all previous rejections have been withdrawn. Therefore, Applicant’s arguments are moot. However, new rejections have been set forth above.
Conclusion
No claims are allowable.
Art of Record:
Westenfelder, US 2008/0241112; Published 2008 (composition for in vivo administration comprising conditioned media from rat-derived MSCs and a carrier).
Prockop et al., US 2013/0039924; Published 2013 (composition for in vivo administration comprising conditioned media from rat-derived MSCs and a carrier).
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 JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G. Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
