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 .
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 80-82 and 94 are 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.
The language “is induced in at least 14 days after contacting” in claim 80 (and similar language in claims 81-82 and 94) is unclear. It is not clear whether the intent is that the state is induced within 14 days after contact, or is not induced until 14 days after contact, or is induced for at least 14 days after contact.1 This makes the scope of the claim indefinite.
Claims 90-95 are 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.
The claims are drawn to “a population of pluripotent stem cells”. However, claim 90 contains language as a process claim: “wherein at least a subset of the one or more transcription factors induce a change in a transcriptomic state of the population of pluripotent stem cells”, “wherein contacting the population”, “induce a change”, “change is detected”, “thereby differentiating the population”. Claim 94 also contains language as a process claim: “wherein the one or more transcription factors induce differentiation of the population of pluripotent stem cells in at least 24 hours following induction of the one or more transcription factors”.
The Federal Circuit decided an issue of first impression - whether a patent claim that covers both an apparatus and method of use of that apparatus passes muster under 35 USC §112, 2nd paragraph (indefiniteness). Defending its "1-click system," Amazon won a summary judgment ruling of invalidity, IPXL Holdings, LLC v. Amazon.com, Inc., 333 F. Supp. 2d 513 (E.D. Va. 2004), which the Federal Circuit affirmed in part (IPXL Holdings LLC v. Amazon.com Inc., 77 USPQ2d 1140 (Fed. Cir. 2005)).
After upholding the district court's claim constructions and affirming the finding that all but one of the asserted claims were anticipated, the Federal Circuit next affirmed the summary judgment of invalidity (for indefiniteness) for the remaining asserted claim, which read:
25. The system of claim 2 [including an input means] wherein the predicted transaction information comprises both a transaction type and transaction parameters associated with that transaction type, and the user uses the input means to either change the predicted transaction information or accept the displayed transaction type and transaction parameters.
Claim 25 on its face was directed to a "system." However, it also recites use steps ("the user uses the input means to ...change the predicted transaction information ... "). This claim was found indefinite by the district court, a decision upheld at the Federal Circuit.
A similar situation exists here, where what is claimed is a population of cells, but embedded within the claim are steps of a process. Moreover, the claim begins with a population of “pluripotent stem cells” but concludes with “differentiated” pluripotent stem cells. A cell cannot be both a “pluripotent stem cell” and “differentiated”.
Applicant is advised to revise the claim to describe only what the population comprises and/or what properties these cells possess.
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 76, 77, 79-95 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. This is a NEW MATTER rejection.
Claims 76, 77, 79-95 were first presented in a preliminary amendment after the filing date.
Claim 76 recites (step a.) “contacting the population of pluripotent stem cells with one or more enzymes and one or more vectors”. Claims 80-82 and 90 repeat the language of contacting cells with one or more enzymes. Claim 83 narrows “enzymes” to “transposases”. However, there is no support in the disclosure as filed to contacting cells with “enzymes” in general, or “transposases” in particular. The specification supports that the cells comprise transposases, but not contacting the cells with transposases. At page 19, lines 33-34, the specification reads: “500,000 to 800,000 hiPSCs were nucleofected with PBAN-TF and Super piggyBAC™ Transposase (SPB: System Biosciences, PB210PA-1)…”. However, this refers to a plasmid (PB210PA-1) encoding a transposase, not to the transposase itself.2
Claim 96 is 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. This is a NEW MATTER rejection.
Claim 96 was first presented after the filing date.
Claim 96 is directed to a “pharmaceutical composition”. The term “pharmaceutical” does not appear in the application as filed.
Claims 76, 77 and 79-96 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.
Independent claim 76 recites “wherein the change in the transcriptomic state of the population of pluripotent stem cells is detected in at least 14% of the population of pluripotent stem cells”.
Independent claim 90 recites “wherein the change [in the transcriptomic state] is detected in at least 14% of the population of pluripotent stem cells”.
Independent claim 96 recites “wherein the change [in the transcriptomic state] is detected in at least 14% of the population of pluripotent stem cells”.
The “14 %” aspect comes from Example 1, beginning on page 16. In this experiment, “The piggyBAC™ vector containing TFs was nucleofected into human induced pluripotent stem cells (hiPSCs), puromycin selection was performed to isolate cells that have stably integrated the TFs, and these cells were expanded and TF overexpression was induced by doxycycline addition for four days (FIG. 1B). Emulsion-droplet-based RNA sequencing, which captures single cells within aqueous droplets containing a barcoded gel with a unique cell barcode, was performed. Libraries were prepared and 401 single cells were sequenced. The overexpressed TFs were detected and identified in only 57 of 401 cells (14.2%, FIG. 1C).”
First, the claims are not limited to “14.2 %”, but recite “at least 14 %”, which would encompass 20%, 50% or even 100%. Therefore, the range “at least 14 %” introduces NEW MATTER.
Second, this “14.2 %” was a result Applicant happened to obtain using a specific set of experimental parameters, outlined in the “Methods” section beginning on page 19. Such specific parameters included a particular cell line, particular cell culture conditions, particular nucleofection conditions (e.g., number of cells, amount of vector DNA, particular reagents), and finally, the measurement of the number of cells expressing the transcription factors was conducted by single-cell sequencing, a procedure having its own set of parameters. The particular transcription factors used in this experiment were not disclosed. In addition, it is noted that the procedure involved transposition of the transcription factor-encoding constructs (by the activity of the Super piggyBAC™ Transposase) into the genomes of individual cells. The particular site in the genome at which a particular construct transposes is not within one’s control.3 The level of expression of a particular integrated construct can be affected by the particular site into which integration occurred. For example, Patel (G3, 2024) states (page 9, right column, first paragraph): “Additionally, because the insertion pattern of the piggyBac transposase is semi-random, variable expression of the integrated transgene could occur as a result of either position effects or copy number variation.”
The 14.2% resulted in this experiment from a myriad of diverse variables and random integration events, yet the claims are not limited to this particular set of variables, undisclosed set of transcription factor-encoding sequences, or insertion sites. Rather, the claims encompass a genus of methods (or cell populations) having this “at least 14 %” property. One of ordinary skill in the art would not be able to predict which of the tens of millions of combinations of the numerous experimental variables, transcription factors and their uncontrollable insertion sites would result in the “at least 14 %” property, and Applicant has not adequately described the genus of such combinations that would result in this “at least 14 %” property. Indeed, based on the random integration aspect alone, one could repeat this experiment exactly as described in the specification (assuming there was more information on the nature of the library of constructs (i.e., the “Individual pDONR-TFs” that were “cloned into pBAN” to produce the “PBAN-TF”; specification page 19, lines 32-33), and get a result higher or lower than 14 %.
Therefore, while Applicant happened to achieve a change in transcriptional state for 14.2 % of the cell population in this particular experiment, the random nature of transposon integration and unpredictable effects of a given integration site upon expression of the exogenous transcription factor does not provide an adequate written description for a generic method of achieving the 14.2 % result.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
1 The term “induced” is construed to refer to an active step of “inducing” the expression of the one or more transcription factors, based on the following language from the specification: “In some embodiments, cells are cultured in the presence of an inducing agent for at least one day (e.g., at least 2 days, at least 3 days, at
least 3 days at least 5 days, at least 10 days or at least 14 days) to induce expression of one or
more transcription factors.”
2 Refer to the PiggyBac™ Transposon Vector System User Manual (page 4) provided with this Office action.
3 The transposase inserts into TTAA chromosomal sites; see PiggyBac™ Transposon Vector System User Manual (page 3) provided with this Office action.