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 .
In view of the decision made regarding the pre-appeal request of 6/20/25, the prosecution has been reopened.
Claims 1, 4-6, and 15-17 are still at issue and under consideration.
Claims 2-3, and 19-20 have been canceled.
Claims 7-14 and 18 remain withdrawn as drawn to non-elected invention.
Applicants' arguments filed on 6/20/25, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
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, 4-6 and 15-17 remain 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.
This is because the phrase “productive and stable” In claim 1 is unclear. As applicant is aware, both of said terms “productive” and “stable” are relative and qualitative and do not constitute any absolute characteristics of the recombinants claimed. In traversal of this rejection, applicant has provided a pre-appeal brief stating the following :
I. With regards to unclarity of the terms “productive" and “stable”, raised by the examiner in the last office action, said 112 second rejection is without merit. This is because in view of applicant, the claim literally states that said characteristics are identified by “using fluorescence detection” as evidenced by the disclosure in for example, paragraphs [0049] and [0053].
Applicant then continues by mentioning that the terms “productive” and “stable” as they relate to recombinants have meaning to those skilled in the art and the meanings for said terms here, is not contrary to that used by the skilled artisan and hence, this rejection should be withdrawn.
II. Regarding the rejections directed to claim 6, applicant mentions that the 3 issues previously raised by the examiner namely, (1) at which step in claim 1, the screening of P. pastoris cells of claim 6 occur, (2) it is unknown if the “one or more heterologous DNA fragments” still encode the target protein or not and (3) the ambiguity of the relationship between the transformed P. pastoris cells of claim 6 and “stable and “productive” recombinants, applicant is of the opinion that none of said 3 issues have anything to do with indefiniteness and those skilled in the art would have no uncertainty regarding any of said issues as the invention is well described in for example [0045].
These arguments were fully considered but were found unpersuasive.
With respect to the argument, I shown above, the examiner maintains that said phrase “productive and stable”, remains ambiguous. To begin with, let us analyze each of said terms “productive” and “stable” individually based on the “meaning” in the prior art and later move on to analyze said terms in combination in the phrase “stable and productive” as referred to be applicant.
With respect to the term “stable” and finding a “meaning” therefor in the relevant art, the term “stable” in public databases (see Eppendorf disclosure, attachment 1), as found by the examiner reveals that a “stable” recombinant is non-transient recombinant capable of retaining the transgene and expressing the transgene for a period of “up to months”. However, instant disclosure fails to mention any time limits, over which its “stable” recombinants retain their transgene. Therefore, in contrast to applicant’s view, the meaning of “stable” in the prior art requires a sustainability time limit during which the transgene remains intact in the chromosome of the recombinant and said information cannot currently be found in the instant disclosure, rendering the term “stable” ambiguous.
Similarly, regarding the phrase “productive recombinant”, said phrase has not been explicitly defined in the disclosure and in the absence of any specific definition, to one of skill in the art merely implies that the recombinant is capable of producing (expressing) the transgene. Nothing more. No specific expression requirements in terms of yield, genetic integrity etc. is associated with said phrase. However, applicant in claim 1 is going through a selection process to identify merely the desired “productive” recombinants but objective basis (measurable parameter) of desirability in “production” remains unclear.
In addition, with respect to each of the terms “stable and “productive”, even in paragraph [0045] which applicant mentioned in his/her arguments, no identification of any threshold value below which, all recombinants, which even fluoresce should be ignored as being non-productive or unstable or both can be found. In page 3 of the last office action, the examiner brought the threshold issue to the attention of applicant (in a slightly different language) but no response was provided to this query. Further, nowhere in the disclosure applicant explained how to distinguish between “only productive but not stable” recombinants and “stable but not productive” recombinants.
Now with regards to the phrase “stable and productive recombinants”, in his/her brief, see page 12, applicant mentions that the specification teaches that the “ consistency of the iLOV fluorescence” from any given recombinant during the production process is indicative of genetic stability. He/she further adds that the iLOV reporter can measure genetic stability. However, even though by measuring fluorescence “productivity” in its absolute sense may be measured, nowhere in the disclosure any mention is made regarding the “consistency of fluorescence” and its relationship to stability and through which specific structural manipulations iLOV reporter (or its coding DNA) is able to measure genetic “stability”. In other words, applicant’s comments raise the following question: if a recombinant shows three times more iLOV fluorescence than another recombinant in the same pool of recombinants, transfected or transformed with an identical DNA encoding a transgene and an identical iLOV coding DNA, will it more be 3 times more stable and if the answer is “yes” how does this occur and what recombinant is used as reference (or control).
Regarding argument II set forth as above, the point is well taken regarding section II(2) above, but once again, considering issue II(1) above, claim 1, does not exclude using GFP coding DNA together with iLOV coding DNA, therefore, examiner’s query is not unreasonable.
Further, regarding issue II(3) in claim 16, it remains unclear if by the relative term “optimal” (see 112 second rejections in the previous office actions) applicant is referring to “productive and stable” (such as a recombinant that does not necessarily show the highest intensity of fluorescence but retains high stability) or merely the most productive recombinant (i.e. a recombinant with the highest intensity of florescence) or some recombinant with different properties. Again here, the term “optimal” as utilized by applicant, implies a selection process which utilizes objective measure(s) but said objective measure(s), including the control recombinants utilized, are not clearly identified.
In summary, for the reasons provided above, in addition to those provided in the last final rejection of 6/3/25, instant claims remain rejected.
Claim 17 remains 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. In claim 17, it appears that the control ( reference) used to measure and compare fusion titer expression is a “randomly selected transformant”. However, applicant in his/her previous response (see page 9 of the response dated 3/3/25) mentioned that all transformants are not necessarily recombinants. Therefore, if the randomly selected transformant is non-recombinant, what does “five fold higher fusion titer” represent and would such titers indicate “a stable and productive recombinant”. Applicant is reminded that the probability of the random transformant instantly referred to in claim 17 being “non-recombinant” is quite high as admitted by applicant in page 12, lines 7-10 of the specification, stating that “of many millions of P. pastoris cells transformed only a few thousand will take up and integrate the DNA fragment within the genome to express the encoded genes”. Appropriate clarification is required.
This issue was also raised by the examiner in the office action of 2/9/23 (in a slightly different language) but no specific response was provided by applicant.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Weidner can be reached at 571-272-3045. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651
/Adam Weidner/SPE, Art Unit 1651