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 .
Election/Restriction
Applicant's election with traverse of Group I: claims 1-8, drawn to a method of producing an engineered Chinese Hamster Ovary cell in the reply filed on 11/03/2025 is acknowledged. The traversal is on the ground that The claims are sufficiently related that their respective classes would be thoroughly cross-referenced, and many of the same classes would be searched regardless of which group of claims was elected. This is not found persuasive because this case requires unity of invention. This application contains claims directed to more than one species of the generic invention. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1. Restriction is required under 35 U.S.C. 121 and 372.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected method, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/03/2025.
The requirement is still deemed proper and is therefore made FINAL.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). Acknowledgment is made of Applicants’ claim for benefit to foreign applications EP20170926.8 filed 04/22/2020.
This application claims the benefit of priority to Patent Application PCT/EP2021/060439. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/EP2021/060439, filed on 04/21/2021.
Information Disclosure Statement
The IDS filed 10/19/2022 has been considered by the Examiner.
Status of Claims
Claims 1-8 are under examination.
Claims 9-10 are withdrawn.
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.
For the record and the purpose of examination, The examiner is interpreting claim 1 as performing the integration of the exogenous nucleic acid within 500kb of the expression-enhancing sequence.
Claims 1-8 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 claim contains 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 re Wands (8 USPQ2d 1400 (CAFC 1988)) the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation." These factors include:
(a) the quantity of experimentation necessary;
(b) the amount of direction or guidance presented;
(c) the presence or absence of working examples;
(d) the nature of the invention;
(e) the state of the prior art;
(f) the relative skill of those in the art;
(g) the predictability of the art; and (h) the breadth of the claims.
In considering these factors for the instant claims:
a) A skilled person in the art could not reasonably perform the method of producing an engineered Chinese Hamster Ovary (CHO) cell with construct “for integration”. A skilled person could not be reasonably expected to find and create all variations of the sequences that fall within the 500kb upstream and 500kb downstream of the enhancer sequence without undue experimentation. The person skilled in the art would need to define a specific region and furthermore how the region is modified.
b) The present application claims a method of producing an engineered Chinese Hamster Ovary (CHO) cell, the method comprising: introducing into a CHO cell a construct for integration of an exogenous nucleic acid molecule into or within 500 kb upstream or downstream of an expression- enhancing sequence in the genome of the cell, the expression-enhancing sequence being at least 90% identical to a sequence selected from any one of SEQ ID NOs: 1-47. The claim does not describe the construct or method of how the exogenous nucleic acid is introduced; therefore, it would not be possible to determine how the CHO cell genome would be edited. Furthermore, the method of integration is not defined, including the method of introducing.
c) The specification does not provide functional examples of the various engineered CHO cells where the exogenous gene is placed in the various positions within 500kb up/downstream or within the various enhancer sequences of claim 1.
d) The nature of the invention, is complex because large variations in exogenous sequences and location would have a large effect on the CHO cell health, viability, as well as protein expression, regulation, and function.
e) Lee et al. teach the importance of site specific integration in CHO cell lines increasing the likelihood of generating isogenic cell lines with consistent protein production (page 1, abstract).
f) The skill of those in the art of genome modification is high, however the broad scope would render difficulty to any practitioner.
g) The predictability of modifying CHO cells is relatively high. However, the various modifications could decrease the predictability of the modification and expression.
h) The claims are broad in that they are drawn to a vast number of regions for modification and further the exogenous sequence integrated could affect cell function.
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 1-8 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: steps to achieve integration.
It is unclear how a construct for integration of an exogenous nucleic acid molecule into or within 500 kb upstream or downstream of an expression- enhancing sequence in the genome of the cell, the expression-enhancing sequence being at least 90% identical to a sequence selected from any one of SEQ ID NOs: 1-47 is intended to limit the method. It is unclear the steps of the method required to achieve integration.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Scientific Reports, 2015) as evidenced by NCBI (Genome Data Viewer).
Regarding claim 1, Lee et al. teach a method of producing an engineered Chinese Hamster Ovary (CHO) cell (page 1, paragraph 2). Lee et al. teach introducing into a CHO cell a construct for integration of an exogenous nucleic acid molecule (page 1, paragraph 2).
Lee et al. do not specifically teach the expression-enhancing sequence is SEQ ID 42 of the present application. Lee et al. teach introduction of an exogenous gene into a CHO cell at the gene LOC100770484 for C1GALT1-specific chaperone 1 which is at position 74,795 - 75,748 as evidenced by NCBI. The insertion site taught by Lee et al. at the gene LOC100770484, thus falls into the expression-enhancing sequence of Seq ID NO: 42 which aligns to positions 61439-85420 of the Chinese Hamster Ovary (CHO) cell.
Regarding claim 2, The expression-enhancing sequence within close proximity is SEQ ID NO: 42.
Regarding claim 3, Lee et al. teach the exogenous nucleic acid molecule is inserted into the gene LOC100770484 for C1GALT1-specific chaperone 1. The placement of this molecule is within 100kb of the expression enhancing sequence.
Regarding claim 4, Lee et al. teach the integration of the exogenous nucleic acid molecule is achieved by CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats)/Cas9 method (page 1, abstract). Lee et al. further teach integration of the exogenous nucleic acid molecule in CHO cells can also be achieved by TALEN (Transcription Activator-Like Effector Nuclease)-based method or ZFN (zinc-finger nuclease)-based method (page 1, introduction.
Regarding claim 5, Lee et al. teach the integration of the exogenous nucleic acid molecule is achieved by CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats)/Cas9 method (page 1, abstract).
Regarding claim 6, Lee et al. teach targeting a total of four sites in three different genomic loci of CHO cells (page 2, results), which reads on the exogenous nucleic acid molecule integrates at two or more integration sites in the genome of the cell.
Regarding claim 7, Lee et al. teach the exogenous nucleic acid encodes high and stable expression of recombinant proteins (page 1, first paragraph).
Regarding claim 8, Lee et al. teach an engineered Cho cell (page 1, paragraph 2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Catherine L McCormick whose telephone number is (703)756-5659. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm.
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635