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/Restrictions
Applicant's election with traverse of Group II, primer pair for Polymerase Chain Reaction (PCR) amplifying a plasmid Ori element; elects the quantitative PCR (qPCR), and further elects the cellular formulation as TCR-T in the reply filed on 8/18/2026 is acknowledged. The traversal is on the ground(s) that the response asserts there is no evidence the kit can be used in materially different methods including kinetics of binding and/or isolation of homologs. This is not found persuasive because this is merely arguments of counsel not substantiated by evidence, isolating homologs or binding kinetics Mehra (Published online 28 June 2005 in Wiley InterScience) teaches kinetic analysis of PCR amplification including primers.
Claims 1-6 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/18/2026.
Priority
The instant application was filed 04/19/2024 and is a divisional of 18351651, filed 07/13/2023, which is a continuation of PCT/CN2022/127776 , filed 10/26/2022.
It is noted the instant application is identified as a divisional. However instant claims 7-17 are drawn to the same invention as claims 6-9 of 18/351651.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 7-17 are objected to because of the following informalities:
Claim 7 is objected to as it recites “Ori” and “KanR” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Claim 7 recites, “Polymerase Chain Reaction.” “Polymerase Chain Reaction” is not a proper noun or the first word of the claim and thus should not be capitalized.
Claim 11 recites, “HEK293 Residual DNA Detection Kit.” “HEK293 Residual DNA Detection Kit” is not a proper noun or the first word of the claim and thus should not be capitalized.
Claim 12 recites, “Real-Time PCR.” “Real-Time PCR” is not a proper noun or the first word of the claim and thus should not be capitalized.
Claim 16 is objected to as it recites “TCR-T, CAR-T, CAR-NK, and CAR-M” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Appropriate correction is required.
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.
Claims 7-17 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.
Claim 7 as amended requires, “A method for evaluating residual host DNA in a cellular formulation, comprising the following steps: (a) quantifying an amount (R1) of residual host DNA in a viral formulation using a DNA residue detection kit; (b) quantifying an amount of a plasmid Ori element and/or a KanR gene (P1) in the viral formulation and of a reference vector omprising the plasmid Ori element and/or the KanR gene by PCR amplification using a primer pair for amplifying a plasmid Ori element and/or a KanR gene and a probe for detecting a plasmid Ori element and/or a KanR gene; (c) quantifying an amount of the plasmid Ori element and/or the KanR gene (P2) in the cellular formulation and in the reference vector by PCR amplification with the primer pair for amplifying the plasmid Ori element and/or the KanR gene and the probe for detecting the plasmid Ori element and/or the KanR gene; (d) determining an amount of the residual host DNA in the cellular formulation (R2) based on a formula R2=R1*(P2/P l).”
Thus the claims encompass quantifying any residual host DNA in ay viral formulation by using any DNA residue kit. This is an enormous genus as it encompasses any viral formulation encompassed by any standard from any species as well as any residual DNA from any species. Further the claims encompass anything which can be considered a DNA residue detection kit.
The claims encompass, “quantifying an amount of a plasmid Ori element and/or a KanR gene (P1) in the viral formulation and of a reference vector omprising the plasmid Ori element and/or the KanR gene by PCR amplification using a primer pair for amplifying a plasmid Ori element and/or a KanR gene and a probe for detecting a plasmid Ori element and/or a KanR gene.” This encompasses any Ori element or any Kan gene from any species in any viral formulation and any reference vector. Further the claim encompass any primer pair and any probe for amplification and detection of any KanR gene or any Ori element.
Wang (Plasmid 61 (2009) 47–51) teaches there at least 30 plasmid origins of replication in bacteria (as of 2009), table 1).
Georghiou (PLOS One (2012) volume 7, issue 3, e33275, pages 1-12) teaches there are numerous kanamycin resistance genes.
Burgin (Journal of Mammalogy, 99(1):1–14, 2018) teaches, “We found 6,495
species of currently recognized mammals.” (page 1, 1st paragraph). Thus limiting the cell sample to just mammals encompasses an enormous genus of species.
Pride (Scientific American (2020) pages 1-20) teaches, “Biologists estimate that 380 trillion viruses are living on and inside your body right now—10 times the number of bacteria.” Thus the claims encompass an enormous genus of virus and bacteria as well.
The claims are limited to the detection of plasmids contamination of viral formulation and cellular formulation by the use of SEQ ID NO 6 and SEQ ID NO 7.
When the claims are analyzed in light of the specification, the invention encompasses an enormous number of nucleotide molecules encompassed by residual host DNA, plasmid Ori, Kan R gene . The specification teaches the use of SEQ ID NO 6 and SEQ ID NO 7 to detect plasmid DNA in viral and cellular formulations produced in laboratories. Thus the teachings of the specification do not teach detection of host cell DNA, but plasmid DNA. Further the specification only teaches detection of plasmid DNA which comprise SERQ ID NO 6-8.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been by full structure. The instant specification teaches detection of host cell DNA, but plasmid DNA. Further the specification only teaches detection of plasmid DNA which comprise SERQ ID NO 6-8.
Next, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (e.g. other nucleotide sequences or positions with in a specific gene or nucleic acid), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case the specification provides the structural limitation no structural limitations of host cell DNA, plasmid, viral formulation or cellular formulation. The claims read in light of the specification encompass any host cell DNA from any host of any species and any cellular formulation and any viral formulation from any species.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed host cell DNA, plasmid, viral formulation or cellular formulation regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993), and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
An adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the '525 patent, "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself." Id. at 1170, 25 USPQ2d at 1606.
In the instant application, the provided information regarding host cell DNA by use of a primer to SEQ ID NO 6, and SEQ ID NO 7 do not constitute an adequate written description of the broad subject matter of the claims, and so one of skill in the art cannot envision the how to detect any host cell DNA, any plasmid, any viral formulation or any cellular formulation. Adequate written description requires more than a statement that nucleic acids with a particular quality are part of the invention and reference to a potential method for their identification.
In conclusion, the limited information provided regarding the breadth of the claimed invent is not deemed sufficient to reasonably convey to one skilled in the art applicants possessed the ability to detect any host cell DNA from any species, any plasmid DNA from any species, any viral formulation from any species or any cellular formulation from any species solely by the use of a “primer” of SEQ ID NO 6 and SEQ ID NO 7
Thus, having considered the breadth of the claims and the provisions of the specification, it is concluded that the specification does not provide adequate written description for the claims.
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 7-17 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.
Claim 7 recites. “(a) quantifying an amount (R1) of residual host DNA in a viral formulation using a DNA residue detection kit.” The specification and claims provide no definition or standard of what is required or encompassed by a DNA residue kit. It is unclear what is required of DNA residue kit. Further the claim is confusing a and unclear in view of the recitation of “viral formulation.” The specification teaches, “A method for detecting residual host DNA in a final cellular or viral formulation of a cellular therapy is provided.” Thus the specification appears to teach cellular and viral formulations are different. However the claim recites both and the specification provide no definition or standard of what is required of viral formulation or cellular formulation. Thus it is unclear what is required of a viral formulation or cellular formulation or how to differentiate the two.
Claim 11 is unclear as the claim recites, “the DNA residue detection kit comprises a HEK293 Residual DNA Detection Kit.” The claim does not provide what is required of HEK293 Residual DNA Detection Kit. However the specification teaches, “The residual host DNA in the viral vector was detected with HEK293 Residual DNA Detection Kit (PCR-Fluorescent Probe Method) (Cat. No: 1101104).” Thus the recitation appears to be a tradenamne. MPEP 2173.05 (u) states, “trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. In fact, the value of a trademark would be lost to the extent that it became descriptive of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to identify or describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name.”
Further claim 6 is confusing as it recites, “detecting a plasmid residue in the cellular formulation (P2) with a primer probe.” The claim later requires the primer probe comprises a sequence of SEQ ID NO 6. The specification does not provide a limiting definition of primer probe. However claim 8 depends from claim 6 and recites, “wherein detecting the plasmid residue in the viral formulation (P1) with the primer probe a comprises the following steps: 1) designing a primer; 2) preparing a quantitative standard comprising at least one of Ori targets or Kan targets with a plasmid vector; 3) preparing a primer probe of an Ori gene or the KanR gene into a primer mixture, adding the primer mixture into an amplification mixture to perform an amplification, and obtaining an amplification standard curve; and 4) calculating the plasmid residue in the viral formulation (P1) in accordance with the amplification standard curve.” Thus it is unclear how claim 8 relates to the primer probe of claim 6. It appears the recitation of SEQ ID NO 6 in claim 6 suggests the primer probe (or primer?) is already designed, thus it is unclear if claim 8 further limits claim 6 and if so how. Similarly claim 9 recites, “wherein the plasmid residue in the cellular formulation (P2) is detected using primers for an Ori gene.” It is unclear how this relates to the primer probe of claim 6. If the primers of claim 8 is the same as the primer probe of claim 6 it is unclear how it further limits as SEQ ID NO 6 appears to be to a sequence of an ORI gene.
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 7-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental step or abstract idea without significantly more. The claim(s) recite(s) the abstract idea or mental step of calculating. . This judicial exception is not integrated into a practical application because if there is no deletion or an amplification or unchanged expression or increased expression no treatment 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 no deletion or an amplification or unchanged expression or increased expression no treatment step is required.
Claim analysis
The instant claim 7 is directed towards a method for evaluating residual host DNA in a cellular formulation, comprising the following steps: (a) quantifying an amount (R1) of residual host DNA in a viral formulation using a DNA residue detection [[Kit]]kit; (b) quantifying an amount of a plasmid Ori element and/or a KanR gene (P1) in the viral formulation and of a reference vector comprises comprising the plasmid Ori element and/or the KanR gene by PCR amplification using a primer pair for amplifying a plasmid Ori element and/or a KanR gene and a probe for detecting a plasmid Ori element and/or a KanR gene; (c) quantifying an amount of the plasmid Ori element and/or the KanR gene (P2) in the cellular formulation and in the reference vector by PCR amplification with the primer pair for amplifying the plasmid Ori element and/or the KanR gene and the probe for detecting the plasmid Ori element and/or the KanR gene; (d) determining an amount of the residual host DNA in the cellular formulation (R2) based on a formula R2=R1*(P2/P l),.
The determining step is mental.
The quantifying steps can broadly be interpreted as reading a report which provides the data.
The quantifying steps could alternatively be interpreted as being active.
Dependent claims set forth further limitations to about primer or primer probe design.
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 step.
With regards to claim 7, the claim recites, “ (a) quantifying an amount (R1) of residual host DNA in a viral formulation using a DNA residue detection [[Kit]]kit; (b) quantifying an amount of a plasmid Ori element and/or a KanR gene (P1) in the viral formulation and of a reference vector comprising the plasmid Ori element and/or the KanR gene by PCR amplification using a primer pair for amplifying a plasmid Ori element and/or a KanR gene and a probe for detecting a plasmid Ori element and/or a KanR gene; (c) quantifying an amount of the plasmid Ori element and/or the KanR gene (P2) in the cellular formulation and in the reference vector by PCR amplification with the primer pair for amplifying the plasmid Ori element and/or the KanR gene and the probe for detecting the plasmid Ori element and/or the KanR gene; (d) determining an amount of the residual host DNA in the cellular formulation (R2) based on a formula R2=R1*(P2/P l),.” These can be interpreted as 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 there is no additional steps which depend from or integrate the judicial exception.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, while the claim has been amended to recite a sequence comprising SEQ ID NO 6, SEQ ID NO 7, and SEQ ID NO 8 is a sequence of ORI which was known and commonly used to detect plasmid contamination.
With regards to the detecting steps of the claims. The specification teaches:
[The residual host DNA in the viral vector was detected with HEK293 Residual DNA Detection Kit (PCR-Fluorescent Probe Method) (Cat. No: 1101104). (0077)Thus the claim does not provide additional steps which are significantly more.
Further the art of Lamers (Blood (2011, volume 117, pages 72-.82), Sack (G3 Genes genomes genetics (2016) volume 6, page 2781-2790) and Wally (Scientific Reports | (2019) 9:1652) teaches detection of plasmid DNA using ORI was routine and conventional.
Summary
Lamers (Blood (2011, volume 117, pages 72-.82), Sack (G3 Genes genomes genetics (2016) volume 6, page 2781-2790), Wally (Scientific Reports | (2019) 9:1652), and Smider (US20040235121) are the closest prior art. However, Lamers, Sack, Wally and Smider do not teach the equation of the claim.
No claims 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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