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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 922/2025 has been entered.
Claim Status and Formal matters
This action is in response to papers filed 9/22/2025.
Claim 1 has been amended.
Claims 1-8 are pending.
Applicant’s election without traverse of GAPDH as the standard gene in the reply filed on 9/17/2024 is acknowledged.
Priority
The instant application was filed 04/14/2023 and is a divisional of 16474164 , filed 06/27/2019, which is a national stage entry of PCT/JP17/46939 with an international filing date: 12/27/2017 and claims foreign priority to JP2016-256279, filed 12/28/2016. The priority document is not in English. Thus the application is being given priority to 12/27/2017.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: Claim 1 has been amended to recite, “an endogenous Plet1 gene,” (c) calculating a control value by dividing the expression level of the endogenous Plet1 gene in the control cell measured in step (a) by the expression level of the standard gene in the control cell measured in step (a) according to the following formula: control value = [the expression level of the endogenous Plet1 gene in the control cell measured in the step (a)] / [the expression level of the standard gene in the control cell measured in step (a)]” Review and searching of the specification did not reveal antecedent basis for “endogenous Plet1.”
Response to Arguments
This is a new ground of objection.
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 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 has been amended to recite, “measuring an expression level of an endogenous Plet1 gene and a standard gene in test cells and expression level of the endogenous Plet1 gene and the standard gene in a control cell, wherein the endogenous Plet1 gene comprising the nucleotide sequence of SEQ ID NO: 1.” Thus the claim appears to be defining SEQ ID NO 1 as the endogenous. However it is unclear how to differentiate an endogenous PLET1 having a sequence of SEQ ID NO 1 from an exogenous having a sequence of SEQ ID NO 1. Review of the specification did not reveal any teachings on how to differentiate endogenous SEQ ID NO 1 from exogenous SEQ ID NO 1. Thus the metes and bounds are unclear.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental steps without significantly more in the absence (e) selecting a test cell in which the relative quantitative value calculated in step (b), orthe relative expression level calculated in step (d), is higher than that of the other test cells. The claim(s) recite(s) the abstract idea or mental step of calculating, selecting and comparing. This judicial exception is not integrated into a practical application because if there is no (e) selecting a test cell in which the relative quantitative value calculated in step (b), or the relative expression level calculated in step (d), is higher than that of the other test cells no producing step is required. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because if there is specific reagent which requires for significantly more.
Claim analysis
The instant claim 1 is directed towards A method for selecting a cell and producing a recombinant protein employing the selected cell, comprising the following steps: (a) measuring an expression level of an endogenous Plet1 gene and a standard gene in test cells and expression level of the endogenous Plet1 gene and the standard gene in a control cell, wherein the endogenous Plet1 gene comprising the nucleotide sequence of SEQ ID NO: 1 and wherein the test cells and the control cell are Chinese hamster ovary (CHO) cells; (b) calculating a relative quantitative value by dividing the expression level of the endogenous Plet1 gene in the test cells measured in step (a) by the expression level of the standard gene in the test cells measured in step (a) according to the following formula: relative quantitative value = [the expression level of the endogenous Plet1 gene in the test cells measured in step (a)] / [the expression level of the standard gene in the test cells measured in the step (a)]; (c) calculating a control value by dividing the expression level of the endogenous Plet1 gene in the control cell measured in step (a) by the expression level of the standard gene in the control cell measured in step (a) according to the following formula: control value = [the expression level of the endogenous Plet1 gene in the control cell measured in the step (a)] / [the expression level of the standard gene in the control cell measured in step (a)]; (d) calculating a relative expression level by dividing the relative quantitative value for the test cells calculated in step (b) by the control value calculated in step (c) according to the following formula:relative expression level = [the relative quantitative value for the test cells calculated in step (b)] / [the control value calculated in step (c)]; and(e) selecting a test cell in which the relative quantitative value calculated in step (b), or the relative expression level calculated in step (d), is higher than that of the other test cells; and(f) producing the recombinant protein using the selected test cell.
The calculating steps (b), (c), and (d) are mental step or abstract idea.
The selecting step (e ) is a mental step or abstract idea and requires comparing.
The measuring step is an active step requiring analysis of a sample.
Dependent claims set forth further limitations to about introducing the recombinant protein.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract idea or mental steps.
With regards to claim 1, the claim recites, “b) calculating a relative quantitative value by dividing the expression level of the endogenous Plet1 gene in the test cells measured in step (a) by the expression level of the standard gene in the test cells measured in step (a) according to the following formula: relative quantitative value = [the expression level of the endogenous Plet1 gene in the test cells measured in step (a)] / [the expression level of the standard gene in the test cells measured in the step (a)]; (c) calculating a control value by dividing the expression level of the endogenous Plet1 gene in the control cell measured in step (a) by the expression level of the standard gene in the control cell measured in step (a) according to the following formula: control value = [the expression level of the endogenous Plet1 gene in the control cell measured in the step (a)] / [the expression level of the standard gene in the control cell measured in step (a)]; (d) calculating a relative expression level by dividing the relative quantitative value for the test cells calculated in step (b) by the control value calculated in step (c) according to the following formula:relative expression level = [the relative quantitative value for the test cells calculated in step (b)] / [the control value calculated in step (c)]; and(e) selecting a test cell in which the relative quantitative value calculated in step (b), or the relative expression level calculated in step (d), is higher than that of the other test cells;.” These are abstract ideas or mental steps.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as in the absence of the relative quantitative value calculated in step (b), or the relative expression level calculated in step (d), is higher than that of the other test cells.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, the single active step requires no specific reagents which provide for significantly more.
With regards to claim 2 the claim requires a single active step of measuring the amounts of nucleic acids. The specification teaches:
[0052]
A method for measuring the expression level of the gene is not particularly limited, and, for example, a method such as quantitative real-time PCR (qPCR), a reverse transcription quantitative real-time PCR (RT-qPCR) method, an expression difference analysis by RNA-seq using NGS, an expression difference analysis using a DNA microarray, Northern blotting, or ELISA (Enzyme-linked Immunosorbent Assay) is exemplified. Among these, the RT-qPCR method can perform rapid measurement, and therefore is preferred. The RT-qPCR method will be described in detail in the section of Examples.
.
Thus the claim does not provide additional steps which are significantly more.
The art of Depreter( Proceedings National Academy of Sciences USA (2008) volume 105, pages 961-966), PREDICTED: Cricetulus griseus placenta-expressed transcript 1 protein-like (LOC100751053), mRNA (https://www.ncbi.nlm.nih.gov/nuccore/354472723?sat=21&satkey=108855981, 10/26/2011), Ferguson (Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor(NY): Cold Spring Harbor Laboratory Press; 2009.Glycosylphosphatidylinositol Anchors, pages 1-10)Chin (US 20090214553) and Yamka (WO2010/009474) demonstrate the active steps of the claim are route and conventional.
Response to Arguments
This is a new ground of rejection.
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.
Claim(s) 1-2, 4, 6-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Depreter( Proceedings National Academy of Sciences USA (2008) volume 105, pages 961-966), PREDICTED: Cricetulus griseus placenta-expressed transcript 1 protein-like (LOC100751053), mRNA (https://www.ncbi.nlm.nih.gov/nuccore/354472723?sat=21&satkey=108855981, 10/26/2011), Ferguson (Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor(NY): Cold Spring Harbor Laboratory Press; 2009.Glycosylphosphatidylinositol Anchors, pages 1-10)Chin (US 20090214553) and Yamka (WO2010/009474).
Claim 1 has been amended to recite, “ wherein theendogenous Plet1 gene comprising the nucleotide sequence of SEQ ID NO: 1.” Thus the broadest reasonable interpretation is SEQ ID NO 1 is endogenous Plet1, as the specification and originally filed claims do not provide for how to differentiate endogenous SEQ ID NO 1 from exogenous SEQ ID NO 1.
With regards to claim 1, Depreter teaches transfection of Plet-1 into CHO cells (Figure 4). Depreter teaches, “ Plet-1 is annotated as having a C-terminal transmembrane (TM) region, and this region is predicted for the mouse1, rat, and hamster sequences using TMHMM. In addition, a GPI anchor was predicted by two independent prediction algorithms in mouse1, rat, and hamster, consistent with reports that the hamster orthologue of Plet-1 is GPI anchored (23). Notably, ‘‘mouse2’’ lacks both the GPI anchor and TMsites (SI Fig. 10), suggesting the existence of a secreted isoform. Other than these features and a number of potential glycosylation sites, we found no known functional motifs in the Plet-1 coding sequence of any species. Although ProSite identified a region of homology with Threonine-rich region/Ig and major histocompatibility complex domain/Type I antifreeze protein containing protein, this was not considered significant because of the high likelihood of this pattern arising by chance.”(page 963, 2nd column, last full paragraph)
Depreter does not specifically teach the sequence of PLET1 (SEQ ID NO 1), normalizing expression of Plet-1 to a standard gene in test cell (step b)and control cell (step c) or determining fold changes in expression of Plet-1 between test cells and control cells or comparing.
However, Chin teaches normalization of target genes to GAPDH to determine a normalized value and calculating a fold change (0108).
PREDICTED: Cricetulus griseus placenta-expressed transcript 1 protein-like (LOC100751053), mRNA teaches Chinese hamster Plet 1 sequence.
Yamka teaches, “The decision on whether a gene is "up" or "down" is based on the fold change, which is calculated as treatment intensity/control intensity for each individual probe.”(00158).
Ferguson teaches, “The replacement of carboxy-terminal transmembrane domains by GPI-addition signal peptides allows their expression on the plasma membrane of transfected mammalian cells in GPI-anchored form. This can be a useful way to produce soluble forms of membrane proteins.” (page 8, top)
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to normalize gene expression of CHO Plet1 to a housekeeping gene such as GAPDH in test cells and control cells, and then compare expression of different test cells by looking at fold increase by dividing the normalized gene expression of test cells by the control samples to select CHO cells for production of recombinant membrane proteins. The artisan would be motivated to determine if expression of CHO Plet1 was increased in different populations of CHO cells to select cells for recombinant expression to produce membrane proteins. The artisan would have a reasonable expectation of success as the artisan is merely using known method to normalize and compare gene expression.
With regards to claim 2, 4, 7 plet1 of Depreter is a recombinant protein as it is transfected into the cell and expressed in the cell.
With regards to claim 6, Yamka teaches gene expression is upregulated if the expression is 2 fold or higher (0158).
Response to Arguments
The response begins traversing asserting the prior art does not specifically suggest the detection of endogenous Plet1. This argument has been thoroughly reviewed but is not considered persuasive as the specification and originally filed claims do no disclosed how to differentiate endogenous Plet1 from exogenous Plet1. However the prior art as cited render obvious the detection of SEQ ID NO 1.
The response further alleges there is no motivation to expression an recombinant protein which is cells with higher expression of Plet1. This argument has been thoroughly reviewed but is not considered persuasive as Depreter teaches Plet1 is a recombinant protein which is more highly expressed in CHO cells in which Plet1 is transfected.
Claim(s) 3,5, 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Depreter( Proceedings National Academy of Sciences USA (2008) volume 105, pages 961-966), PREDICTED: Cricetulus griseus placenta-expressed transcript 1 protein-like (LOC100751053), mRNA (https://www.ncbi.nlm.nih.gov/nuccore/354472723?sat=21&satkey=108855981, 10/26/2011), Ferguson (Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor(NY): Cold Spring Harbor Laboratory Press; 2009.Glycosylphosphatidylinositol Anchors, pages 1-10)Chin (US 20090214553) and Yamka (WO2010/009474).as applied to claims 1-2, 4, 6-7 above, and further in view of Baldi (Biotechnol Lett (2007) 29:677–684).
Depreter, Ferguson, Chin, and Yamka teach the transfection of Plet1 in CHO cells and comparison to control cells.
Depreter, Ferguson, Chin, and Yamka do not specifically teach the transfection of PLEt1 into control and test cells or producing recombinant antibodies.
However, Baldi teaches a review of recombinant protein production in mammalian cells(title). Balki teaches transfection efficiencies is a major source of variability in expression and protein production. (682, 2nd column, top). Balki teaches the use of CHO cells for production of antibodies (table 1).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to examine expression of recombinant Plet1 in control cells and test cells treated to produce recombinant antibodies. The artisan would be motivated to examine the variability in transfection and/or expression of PLET1 and recombinant antibodies in the CHO cells. The artisan would have a reasonable expectation of success as the artisan is merely using known methods to screen clones.
Response to Arguments
The response traverses the rejection for the arguments set forth with respect to the independent claim. These arguments are not persuasive for the reasons of record.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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