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 .
Status of the claims
This action is in response to the communication of 4/26/2023
Claims 1-9 are pending.
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 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.
Claim 1 and 6 includes the phrase “pancreatic progenitor cell population or a cell population at a later stage of differentiation”.
This phrase could reasonably have two contradictory interpretations for “cell population at a later stage of differentiation”. The first interpretation could be a cell population that is at a later stage of differentiation towards an insulin-producing cell than a pancreatic progenitor cell. The second definition could be that cell population at a later stage of differentiation could be any cell that has begun the process of differentiation (i.e., any stage after pluripotent stem cell).
The specification gives a definition of the term in [0055] as “In the present invention, ‘pancreatic progenitor cell population or cell population at a later stage of differentiation’ means a pancreatic progenitor cell population or an endocrine progenitor cell population or means both a pancreatic progenitor cell population and an endocrine progenitor cell population.” Or in other words, “a pancreatic progenitor cell population means a pancreatic progenitor cell population”, which isn’t incredibly instructive when determining the meaning “or cell population at a later stage of differentiation”. In [0007] the spec recites “the pancreatic progenitor cell population or the cell population at a later stage of differentiation is a cell population produced by the induction of differentiation from pluripotent stem cells.” (Emphasis added).
So, reasonably there may be two different interpretations of this phrase, such that the skilled artisan may not be apprised of the actual scope of the claim. Thus, the claim is indefinite.
For purposes of claim interpretation, “cell population at a later stage of differentiation” will be interpreted as any cell that has differentiated beyond a pluripotent stem cell towards becoming an insulin-positive cell.
Regarding claims 2 and 7, The term “substantially no ALK5-inhibiting activity” is a relative term which renders the claim indefinite. The term “substantially no ALK5-inhibiting activity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The specification does however include a somewhat contradictory definition of this term in paragraph [0047]. “’Have substantially no ALK5-inhibiting activity’ not only means that the medium has no ALK5-inhibiting activity but includes the case where the inhibition rate against ALK5 is less than 50%, preferably 40% or less, more preferably 30% or less, further preferably 20% or less, still further preferably 10% or less, especially preferably 5% or less.”
So, it appears that that “substantially no” activity is defined as meaning both “no activity” but could also mean the inhibition rate against ALK5 is less than 50%.
For purposes of examination, it appears that the issue is that certain CDK8/19 inhibitors also have some marginal inhibitory effect on ALK5. So, the broadest reasonable interpretation of this claim will be that “substantially no” inhibiting activity spans from 0% inhibiting activity compared to a control to 49% inhibiting activity. Realistically this would include the scenario where the medium comprises a CDK8/19 inhibitor but no dedicated ALK5 inhibitor is present.
Claims 2-5 and 7-9 are rejected for being dependent on an indefinite claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Yamazoe
Claims 1-2 and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Yamazoe CA3097962A1
Regarding claim 1 and 6, Yamazoe teaches a method for the differentiation of pluripotent stem cells into insulin positive pancreatic B-cells. Yamazoe’s method includes six steps, and on step 4 Yamazoe induces the differentiation of posterior foregut cells into pancreatic progenitor cells (Yamazoe [0058]). In this step, Yamazoe’s differentiation medium includes a factor having CDK8/19-inhibiting activity. Technically based on the claim interpretation, these posterior foregut cells would read on the “later stage of differentiation” cells of claim 1.
In the interest of compact prosecution, Yamazoe also reasonably reads on differentiating a “pancreatic progenitor cell population” too. Technically speaking these foregut cells mature into pancreatic progenitor cells in the process of Yamazoe’s step 4. Thus, during Yamazoe’s step 4 there would reasonably be at least some “pancreatic progenitor cells” present and continuing to differentiate to some degree that in a differentiation medium comprising CDK8/19 inhibitor, or that some residual CDK8/19 inhibitor may still be present in the medium as the process proceeds to steps 5 and 6.
Regarding claim 2 and 7, Yamazoe teaches supplementing their media with ALK5 inhibitor, but in step 5 but does not specifically say to what degree ALK5 is inhibited in their medium. The crux of the rejection for claim 1 is that essentially every element of the claim exists in step 4 of Yamazoe. Yamazoe adds ALK5 inhibitor, but only after step 4. So, for a period of time, Yamazoe teaches a method for producing an insulin-positive cell population comprising differentiating a cell population at a later stage of differentiation (posterior foregut cells) containing a CDK8/19 inhibitor and no ALK5-inhibitor added other than CDK8/19 itself which has marginal ALK5-inhibiting activity. In effect step 4 has “substantially no ALK5-inhibiting activity” per the term’s definition.
In other words, once Yamazoe adds ALK5 inhibitor in step 5, Yamazoe’s method is outside the scope of claim 2 and 7. But during step 4, Yamazoe reads on claims 2 and 7.
Regarding claim 5, Yamazoe’s cell population is produced by the induction of differentiation from pluripotent stem cells. (Yamazoe [0058-0059]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Yamazoe and Hofmann
Claims 1-9 are rejected under 35 U.S.C. 103 as being obvious over:
Yamazoe CA3097962A1, and
Hofmann et al., Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance. Mol Cancer Ther. 2020 Apr;19(4):1018-1030
Claims 1-2 and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamazoe CA3097962A1
Regarding claim 4 and 9, Yamazoe teaches that in their disclosure, a "factor having CDK8/19-inhibiting activity" means any substance having the inhibitory activity for CDK8/19. Yamazoe does not specify exactly which CKF8/19 inhibitor that they used.
Hoffman teaches that BI-1347 is a CDK8/19 inhibitor, and is used for therapeutic purposes to treat cancer. (Hoffman, Abstract). BI-1347 is another name for 2-(4-(4-(isoquinolin-4-yl)phenyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use Hoffman’s known BI-1347 CDK8/19 inhibitor as the CDK8/19 inhibitor of per Yamazoe’s method. One of ordinary skill in the art would have been motivated to do so, since this combination would be combining prior art elements according to known methods to yield predictable results (MPEP 2143 (I) (A)). Yamazoe teaches that “any substance having inhibitory activity” for CDK8/19 may be used, and Hoffman teaches that BI-1347 was a known CDK8/19 inhibitor before the effective filing date of the invention.
One of ordinary skill in the art would have had a reasonable expectation of success, since Yamazoe teaches that essentially any CDK8/19 inhibitor would be acceptable for use in their method.
Regarding claim 3 and 8, Yamazoe teaches the use of an CDK8/19 inhibitor in their differentiation medium. (Yamazoe [0089]). Yamazoe teaches that the concentration of this inhibitor is preferably 0.00001 M to 1 M, and preferably attains inhibitory activity of 50% or more for CDK8/19. (Yamazoe [0081]).
The specification discloses that they tested BI-1347’s (compound 2) IC50 against ALK5. I.e., measuring an inherent property (the IC50) of an existing compound against ALK5. The specification discloses that the IC50 of BI-1347 happens to be greater than or equal to 1µM. -(Spec. [0157-0158])
Since it would be obvious to use BI-1347 as the CDK8/19 inhibitor as explained in the analysis of claim 4, it would be reasonable that BI-1347 in that composition would have the same IC50 towards any substance, including ALK5.
As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that in at least the instance where the composition of claim 1 uses BI-1347 as the CDK8/19 inhibitor, that CDK8/19 inhibitor will have the same IC50 against ALK5 since an IC50 of an inhibitor is essentially a physical/chemical property of that chemical. In other words, that is a fixed value for CDK8/19’s activity against ALK5.
Conclusion
Claims 1-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
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/THOMAS R. AMICK/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638