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 .
Response to Arguments
In the Response, dated 12/23/2025, the Applicant provided amendments to the claims, amendments to the specification, and arguments drawn to the rejection of the previous Office Action. The amendments to the claims and specification have provided for a withdrawal of the objections to the claims and specification; additionally, the claim amendments provide for a withdrawal of the 35 USC 112(b) rejections.
On page 10 of the Applicant’s Arguments, the Applicant states that Jeppesen does not disclose profiles that correlate to individual responses. It is unclear what the Applicant is referring to, since Jeppesen literally states that the method “using spheroids from five patients demonstrated individual response profiles.” See page 1, “Abstract” section.
On pages 10 and 11 of the Applicant’s Arguments, the Applicant states that Jeppesen does not disclose sol-gel that transitions at a range from 0 to 35 °C. Jeppesen teaches Matrigel culture, wherein the material is gelled at 37 °C. See page 3, “Spheroid growth” section. First, it must be noted that Jeppesen’s sol-gel is entirely consistent with the claimed sol-gel, and fulfills the definitions found in the specification. Second, although it is noted that Jeppesen polymerizes the Matrigel at a temperature that is slightly above the claimed value, Jeppesen teaches an identical material as that claimed, with identical physical properties. As such, the claimed range of sol-gel transition temperatures must be entirely consistent with that of the Matrigel is Jeppesen. See the instant specification, page 20, lines 26-31 [bridging to page 21, lines 1-7]). If the Applicant used a sol-gel that is different than that of Jeppesen, with a different transition temperature, this should be explicitly claimed. However, since it appears clear that the Matrigel of Jeppesen can be considered one of the materials consistent with the claimed sol-gel, Jeppesen must also anticipate this limitation.
On page 11 of the Applicant’s Arguments, the Applicant states that Jeppesen generates the spheroids prior to placing them into the sol-gel, whereas the instantly claimed method provides for the step of directly generating the spheroids in the sol-gel. The Applicant is correct in this assessment, and as such, the claims are considered obvious over the cited prior art, since there is nothing disclosed in the arguments or instant specification to suggest that separating the steps or performing them together would result in a functionally different test. Unless the Applicant can provide reasonable evidence to suggest that the modification in the step provided by Jeppesen results in an unexpected improvement in the method’s results, the modification can be considered obvious. This can be considered obvious because the spheroid, the object used to “predict efficacy” is fundamentally the same.
On page 12 of the Applicant’s Arguments, the Applicant reiterates the arguments provided in pages 10 and 11. These were discussed above.
On page 13 of the Applicant’s Arguments, the Applicant underscores that the claimed method is effective for predicting chemotherapeutic efficacy/resistance. As discussed above, this was the explicit purpose provided by Jeppesen in the abstract of the paper [“Chemosensitivity screening using spheroids from five patients demonstrated individual response profiles,” see page 1, “Abstract” section]. The Applicant has provided no clear rationale or excerpts to suggest that Jeppesen did not teach the claimed individualized testing.
On pages 13 and 14 of the Applicant’s Arguments, the Applicant has selected very specific examples in Jeppesen to seemingly suggest that Jeppesen should not be considered enabled. If the Applicant is arguing lack of enablement, it is unclear what specifically claimed limitations allow for the claimed method to be enabled, but Jeppesen is not. If there are enablement shortfalls that exist in Jeppesen, and there are no claim limitations provided to transition over these hurdles, the instant claims must also possess the same issues of enablement. Regardless, Jeppesen explicitly states: We have demonstrated that chemosensitivity testing is possible using … tumor spheroids derived from both primary colorectal tumors and metastases.” See page 14, last paragraph. Therefore, while the Applicant may read Jeppesen in a particular manner, Jeppesen is quite clear on the enablement of the method. If the Applicant believes otherwise, either reasonable evidence should be provided, or other claim limitations that provide for the alleged enablement should be included.
On pages 15 and 16 of the Applicant’s Arguments, the Applicant reiterates some of the previous arguments, with respect to other claim rejections. These have been discussed above.
Based upon the amendments to the claims and specification, all of the objections are withdrawn. Additionally, the claim amendments have provided for a withdrawal of the 35 USC 112(b) rejections. Further, as a result of the amendments to the independent claim, all of the 35 USC 102(a)(1) rejections have been modified into 35 USC 103 rejections. All of the previous 35 USC 103 rejections are maintained for the reasons provided above, and in the previous rejections.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-7, 10-12, 15, 16 and 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over Jeppesen, et al (PLoS One, 12, e0183074, 2017 [IDS Reference]). Jeppesen teaches methods of testing one or more chemotherapeutic agents, including platinum chemotherapeutics, on organoids for colorectal cancer models. See page 1, “Abstract” section. This testing would necessarily inform the relevant audience about the efficacy of the chemotherapeutic, and the cancer’s specific resistance to said chemotherapeutic.
Jeppesen provides a colorectal cancer biopsy, which is considered to be considered to be consistent with the claimed “colon cancer.” Jeppesen dissociates the biopsy into single cells, then prepares the single cell suspension into “organoids,” which by definition, are 3-dimensional tumoroids consistent with the claimed tumoroids. See page 2 and 3, “Materials and Methods” section. Jeppesen provides for chemosensitivity testing on the cancer tumoroids, wherein Jeppesen treats the organoids, individually or in combination with platinum and non-platinum chemotherapeutic agents. See page 5, “Chemosensitivity testing” section. Jeppesen shows data that provides for efficacy and resistances to said chemotherapeutic. See page 12, Figure 6.
Jeppesen teaches Matrigel culture, wherein the material is gelled at 37 °C. See page 3, “Spheroid growth” section. First, it must be noted that Jeppesen’s sol-gel is entirely consistent with the claimed sol-gel, and fulfills the definitions found in the specification. Second, although it is noted that Jeppesen polymerizes the Matrigel at a temperature that is slightly above the claimed value, Jeppesen teaches an identical material as that claimed, with identical physical properties. As such, the claimed range of sol-gel transition temperatures must be entirely consistent with that of the Matrigel is Jeppesen. See the instant specification, page 20, lines 26-31 [bridging to page 21, lines 1-7]).
Jeppesen generates the spheroids prior to placing them into the sol-gel, whereas the instantly claimed method provides for the step of directly generating the spheroids in the sol-gel. However, there is nothing disclosed in the instant specification to suggest that separating the steps or performing them together would result in a functionally different test. The instantly claimed spheroid is considered an obvious variant of Jeppesen’s, because the spheroid, the object used to “predict efficacy,” appears to be fundamentally the same. Unless the Applicant can provide reasonable evidence to suggest that the modification in the step provided by Jeppesen results in an unexpected improvement in the method’s results, the modification can be considered obvious.
With respect to claims 1, 3, Jeppesen teaches the claimed method, wherein the claimed method utilizes an obvious functional variant of the claimed spheroid.
With respect to claims 4 and 5, Jeppesen teaches metastases and explicitly states efficacy with colorectal tumors and metastases. See page 14, last paragraph. This would suggest that Jeppesen likely tested metastases of colorectal tumors. However, if it can be demonstrated that this was not present in Jeppesen, it would be exceptionally obvious to the ordinary artisan that metastases of colorectal cancer would be viable in the method.
With respect to claims 6 and 7, Jeppesen teaches the platinum-based chemotherapeutic oxaliplatin. See page 5, “Chemosensitivity testing” section.
With respect to claims 10 and 11, Jeppesen provides for tissue fragments that are no smaller than 30 µm. See page 3, “Spheroid preparation and culture” section.
With respect to claim 12, as discussed in the rejection of claim 11, Jeppesen teaches tissue diameter that is no small than the claimed lower limit (30 µm). See page 3, “Spheroid preparation and culture” section. As such, it stands to reason that Jeppesen provides for the same number of cells per fragment as that claimed. If there is evidence to suggest that Jeppesen does not anticipate the claimed number, unless evidence is provided to the contrary, the claimed number does not appear to provide for unexpected results, and as such, would be considered an obvious variant of Jeppesen.
With respect to claim 15, Jeppesen teaches Matrigel, and indicates that it polymerizes in response to a temperature change. See page 3, “Spheroid growth” section. Based upon the instant specification, this appears to be consistent with the claimed limitation.
With respect to claims 16, 19 and 20-24, Jeppesen shows a reduction of tumoroid size in response to chemotherapeutics. See page 12, Figure 6. If Jeppesen does not specifically describe the claimed analysis, it would be clear to the ordinary artisan to provide the claimed analysis, based upon the provided data and the expected knowledge of the ordinary artisan.
With respect to claim 25, Jeppesen teaches combined treatments. See page 5, “Chemosensitivity testing” section.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Jeppesen, et al (PLoS One, 12, e0183074, 2017 [IDS Reference]) and Negrei, et al, (Frontiers in Pharmacology, 7(172), 2016).
With respect to claims 8 and 9, Jeppesen teaches 5-FU, oxaliplatin, SN38, and the combination chemotherapeutics FOLFOX (5-FU and oxaliplatin) and FOLFIRI (5-FU and SN38). See page 5, “Chemosensitivity testing” section. Jeppesen does not explicitly teach folinic acid, or a combination of three or more chemotherapeutics. However, when considering the prior art, and the breadth of knowledge expected of the ordinary artisan, it would be obvious to use the claimed combination, because this is already a well-known combination of treating colorectal cancers. See Negrie, page 1, “Abstract” section; MPEP 2141.03.
Conclusion
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 DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651