DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed and Arguments/Remarks, filed 09 June 2026, have been entered. Claims 1-16 are currently pending. Claims 1, 6, 7,12, 13, 15, and 16 are independent claims.
Applicant’s election without traverse of the invention of Group I, drawn to a cisplatin resistant xenograft model for nasopharyngeal carcinoma and a cell line derived from the cisplatin-resistant NPV PDX, is acknowledged.
Additionally, Applicant’s election of the following species:
STR profile of at least one genome DNA locus as set forth in Table 1: vWA, which comprises heterozygous alleles of 14 and 17 repeats in each of the three profiles presented in Table 1,
without traverse is acknowledged.
Claims 7-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-6 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application, U.S. Application No. 18/597,181, filed 06 March 2024, claims priority to U.S. Provisional Application No. 63/488,525, filed 06 March 2023.
Thus, the earliest possible priority for the instant application is 06 March 2023.
Information Disclosure Statement
The information disclosure statement filed 24 June 2024 has been considered by the Examiner.
Claim Objections
Claims 2 and 4 are objected to because of the following informalities: Claims 2 and 4 each reference Table 1 in line 2 of each claim. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(s). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-6 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.
Independent claim 1 recites, “comprising a patient-derived xenograft (PDX) having a short tandem repeat (STR) DNA genomic profile derived from a NPC patient” in line 3, which has multiple issues of indefiniteness.
Firstly, the claim is indefinite because it is unclear whether the PDX is meant to be derived from an NPC patient or whether the STR DNA genomic profile is meant to be derived from an NPC patient.
Secondly, to the extent that the PDX is meant to be derived from an NPC patient, it is unclear whether Applicant intends to encompass that the PDX is specifically derived from the tumor cells/tissue of the NPC patient’s NPC tumors or any cell/tissue isolated from the NPC patient.
Thirdly, to the extent that the STR profile is meant to be derived from an NPC patient, it is unclear whether the STR profile being derived from the patient is meant to encompass alterations or derivations occurring within the STR profile as a result of the PDX development or meant to encompass altering an STR profile of an NPC PDX to match the STR profile of an NPC patient.
As such, the metes and bounds of the claim cannot be determined.
Claims 2-6 each recite “[t]he cisplatin-resistant NPC PDX according to claim” 1 or 2 in line 1 of each claim, which is indefinite because claim 1 is directed to “A cisplatin-resistant xenograft model for nasopharyngeal carcinoma (NPC)” and not to a cisplatin-resistant NPC PDX. As such, the metes and bounds of the claims cannot be determined.
Claim 2 recites, “a STR profile of at least one genome DNA locus” in lines 1-2, which is indefinite because it is unclear whether the recited “a STR profile of at least one genome DNA locus” of claim 2 is meant to be the “a short tandem repeat (STR) DNA genomic profile” recited in claim 1, upon which claim 2 depends. As such, the metes and bounds of the claim cannot be determined.
Claim 3 recites the limitation "the at least one genome DNA" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 3 is dependent on claim 2, which recites “a STR profile of at least one genome DNA locus”. Therefore, “at least one genome DNA” as recited in claim 2 is an adjective modifying “locus”. None of claims 1, 2, nor 3 recite an at least one genome DNA as a noun which can further comprise additional loci. As such, the metes and bounds of the claim cannot be determined.
Claim 4 has multiple additional issues of indefiniteness.
Claim 4 recites, “a short tandem repeat (STR) profile genome DNA” in lines 1-2, which is indefinite because it is unclear whether the “a short tandem repeat (STR) profile genome DNA” of claim 4 is meant to be the same as the “a short tandem repeat (STR) DNA genomic profile” recited in claim 1, upon which claim 4 depends. Additionally, “a short tandem repeat (STR) profile genome DNA” is grammatically indefinite in that it lacks clarity as to what terms are meant to be modifying and which are meant to serve as the noun being modified.
The term “substantially” in claim 4 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, it is unclear to what extent a genomic STR profile must match the profiled displayed in Table 1 to constitute “substantially as shown”.
As such, the metes and bounds of the claim cannot be determined.
Claim 6 recites “derived from” in line 1, which is indefinite because it is unclear to what extent and in what ways the cell line is meant to be derived from the cisplatin-resistant NPC PDX and the metes and bounds of all possible derivatives cannot be determined. For example, it is unclear whether Applicant intends to encompass cells isolated from the cisplatin-resistant NPC PDX and grown in culture or whether Applicant intends to encompass modifications of the cisplatin-resistant NPC PDX cells which facilitate growth in culture or other potentially desired characteristics. As such, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. [2022, Cancer Research, 82(12_Supplement), abstract no. 6021]; as evidenced by Lin et al. [2018, Nature Communications, 9, 4663, 1-17, including supplement, IDS] and Weiss et al. [2018, Journal of Virology, 92(2), e01466-17, 1-19].
Although this reference includes the inventors of the instant application, namely Victor Ho Fun Lee and Ka Yee Li, it does not qualify for a grace period exception, and therefore qualifies as prior art under 35 U.S.C. 102(a)(1), because it lists authors who are not listed as inventors on the instant application, namely, Katie Sze Wai Fung, Chanping You, Yim Ling Yip, and George Sai Wah Tsao. See MPEP 2152.05.
Regarding claim 1, Li teaches a cisplatin resistant xenograft model for nasopharyngeal carcinoma (NPC) comprising a patient-derived xenograft (PDX) (i.e., Xeno76-CR) derived from an NPC patient and having a genomic short tandem repeat (STR) profile derived from an NPC patient [¶ 1].
Regarding claims 2-4, Li teaches wherein the EBV-positive Xeno76 NPC PDX was previously established and used to develop the cisplatin-resistant Xeno76-CR [¶ 1], but does not explicitly teach wherein the Xeno76 or Xeno76-Cr have genomic STR profiles substantially as shown in instant Table 1.
However, Lin teaches the genomic STR profile for Xeno76, which is the EBV-positive NPC PDX used by Li and converted into the cisplatin-resistant EBV-positive NPC PDX, wherein the Xeno76 NPC PDX comprises a genomic STR profile substantially as shown in Table 1, such that the only difference between the 16 loci STR profile of Xeno76 taught by Lin and the same 16 loci STR profile of Xeno76 as presented in instant Table 1 is the second allele for D21S11 which is 32.2 in Lin and 33.2 in instant Table 1 [Supplementary Table 1]. Therefore, Lin provides evidence that the Xeno76 used by Li to generate the Xeno76-CR NPC PDX has a genomic STR profiles substantially as shown in instant Table 1, and as such, the ordinarily skilled artisan at the time of filing the instant application would expect, absent evidence to the contrary, that the cisplatin-resistant derivative of Xeno76 would likewise have a genomic STR profile substantially as shown in instant Table 1. Therefore, Lin teaches an inherent property of the cisplatin-resistant Xeno76-CR NPC PDX taught by Li.
“When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Regarding claim 5, Lin teaches wherein the Xeno76 NPC PDX is EBV positive and wherein the Xeno76 EBV strain is phylogenetically similar to EBV strains Akata, B95-8, Mutu, GD1, C666-1, M81, and GD2, but more distant from EBV strain AG876 [abstract, Figure 2, 8, 9], but does not explicitly teach wherein the Xeno76 EBV strain is EBV-1.
Weiss teaches wherein EBV strains Akata, B95.8, Mutu, GD1, C666-1, M81, and GD2 are all EBV type 1/EBV-1 strains and wherein AG876 is an EBV type 2 strain [Figure 2]. Therefore, by teaching a close phylogenetic relationship between the EBV strain in Xeno76 and a variety of known EBV-1 strains, wherein the Xeno76-derived EBV is more distantly related to a known EBV-2 strain, Lin is teaching wherein Xeno76 is EBV-1 positive, and as such, the cisplatin-resistant Xeno76-CR NPC PDX taught by Li is inherently an EBV1-positive NPC PDX.
Accordingly, by teaching all of the limitations of claims 1-5, Li anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. [2018, Nature Communications, 9, 4663, 1-17, including supplement, IDS]; in view of Miao et al. [2021, American Journal of Cancer Research, 11(3), 640-667] and Weiss et al. [2018, Journal of Virology, 92(2), e01466-17, 1-19].
Regarding claims 1-3, Lin teaches a xenograft animal model for nasopharyngeal carcinoma (NPC) comprising a patient-derived xenograft (PDX) derived from an NPC patient and having a short tandem repeat (STR) DNA genomic profile also derived from the NPC patient, wherein the STR profile comprises the elected genotype of 14, 17 at the vWA locus [abstract, pg 2 col 2 ¶ 2, Supplementary Table 1].
Lin does not teach wherein the NPC PDX is cisplatin resistant.
Miao teaches the development of cisplatin-resistant NPC xenografts [abstract]. Miao also teaches that radiation therapy combined with cisplatin-based chemotherapy is still the main treatment for NPC, but that recurrence rates after primary treatment range from 15-58% with poor survival rates for recurrent or metastatic NPC [pg 640 col 1 ¶ 1- col 2 ¶ 1]. Miao also teaches that resistance to chemotherapy occurs either initially or later after the first line of chemotherapy and that few clinical trials have assessed the intrinsic and acquired resistance to chemotherapy drugs, especially cisplatin, such that treatment options after first-line chemotherapy failure are scarce [pg 640 col 1 ¶ 1]. Miao teaches that therefore, clarifying the mechanism of chemo-resistance in NPC will contribute to early diagnosis, developing appropriate therapy, and improving survival and quality of life for NPC patients [pg 641 col 1 ¶ 1]. Miao further teaches the establishment of cisplatin-resistant NPC cell lines and xenograft mouse models to better understand the molecular mechanisms of drug resistance in NPC [pg 641 col 1 ¶ 4]. Therefore, given the teachings of Miao, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to induce cisplatin resistance in an NPC xenograft model to better understand the molecular mechanisms of cisplatin resistance in NPC.
Regarding claim 4, Lin teaches wherein the NPC PDX comprises a genomic STR profile substantially as shown in Table 1 for the Xeno76 sample, wherein the only difference between the 16 loci STR profile of Xeno76 taught by Lin and the same 16 loci STR profile of Xeno76 as presented in Table 1 is the second allele for D21S11 which is 32.2 in Lin and 33.2 in instant Table 1 [Supplementary Table 1].
Regarding claim 5, Lin teaches wherein the NPC PDX is EBV positive and wherein the Xeno76 EBV strain is phylogenetically similar to EBV strains Akata, B95-8, Mutu, GD1, C666-1, M81, and GD2, but more distant from EBV strain AG876 [abstract, Figure 2, 8, 9], but does not explicitly teach wherein the EBV strain is EBV-1.
Weiss teaches wherein EBV strains Akata, B95.8, Mutu, GD1, C666-1, M81, and GD2 are all EBV type 1/EBV-1 strains and wherein AG876 is an EBV type 2 strain [Figure 2]. Therefore, by teaching a close phylogenetic relationship between the EBV strain in Xeno76 and a variety of known EBV-1 strains, wherein the Xeno76-derived EBV is more distantly related to a known EBV-2 strain, Lin is teaching wherein Xeno76 is EBV-1 positive.
Regarding claim 6, Lin teaches development of a patient-derived EBV positive cell line NPC43 [pg 2 col 1 ¶ 3], but does not specifically teach deriving a cell line from the NPC PDX. However, Lin also teaches wherein most if not all of the other previously reported NPV cell lines have lost their EBV episomes and became EBV negative upon in vitro propagation and that the scarcity of in vitro and in vivo NPC models represents major challenges for NPC and EBV research [pg 2 col 1 ¶ 2]. Lin further teaches wherein the establishment and characterization of new NPC PDX and cell lines will provide valuable experimental tools for NPC and EBV research [pg 2 col 1 ¶ 4]. Therefore, Lin teaches the motivation for an ordinarily skilled artisan to derive a cell line from an EBV positive NPC sample to provide valuable experimental tools for both NPC and EBV research.
Given the motivation taught by Maio to induce cisplatin resistance in an NPC xenograft model to better understand the molecular mechanisms of cisplatin resistance in NPC; and the motivation taught by Lin to derive a cell line from an EBV positive NPC sample to provide valuable experimental tools for both NPC and EBV research; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the NPC PDX of Lin to exhibit cisplatin resistance and to derive a cell line from the cisplatin resistance NPC PDX generated thereby with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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