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 .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US21/73059, filed
21 December 2021. Acknowledgment is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63128294, filed 21 December 2020.
Status of the Claims
Applicant’s preliminary submission filed 26 December 2023 has been entered. Claims 1-10, 13-16, 18-20, 22-24, and 41 are pending. Claims 5-7, 13, 15, 18-19, and 22 have been amended, while claims 11-12, 17, 21, 25-40, and 42-75 have been cancelled without prejudice. Therefore, prosecution on the merits commences for claims 1-10, 13-16, 18-20, 22-24, and 41.
Specification
The substitute Specification filed 21 June 2023 is acknowledged and entered into the application filed.
The lengthy Specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the specification.
However, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, particularly in Paragraph [00181] and the listing of references on Pages 101 (Qi et al) and 104 (Zhao et al, 2015). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 3-4 and 16 are objected to because of the following informalities:
Regarding claims 3-4: Instant claim 3 requires the p53 gene therapy to comprise “restoration and/or amplification of p53 function by gene editing” (emphasis added). Instant claim 4 is dependent upon parent claim 3, and requires the gene editing to comprise using “ZFN, TALEN, or CRISPR to express p53” (emphasis added). The instant claims are objected to for the discrepancy between “function” and “expression”, as Applicant has support for gene editing to express p53 but not have support for the p53 function. See, for instance, Paragraph [0013] of the instant Specification.
Appropriate correction is required.
Regarding claim 16: The instant claim is objected to for failing to recite “or”, or the like, between the recitation of “a vesicular stomatitis viral vector” and “a polyoma viral vector”.
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 1-10, 13-16, 18-20, and 22-24 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 claims contain 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.
The instant claims are directed to a method of treating a pathogenic infection in a subject, comprising administering a therapeutically effective amount of a p53 gene therapy to a subject infected or suspected of being infected by a pathogen. A review of the Specification shows that Applicant has not provided sufficient description of the invention to support they were in possession of a p53 gene therapy that can be administered to a subject infected or suspected of being infected by a pathogen in order to treat said pathogenic infection within the subject.
Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998). Although working examples are not required, the claimed invention is required to be enabled so that any person skilled in the art can make and use the invention without undue experimentation. See MPEP § 2164.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP § 2164.01.
Nature of the invention: Independent claim 1 is directed to a method of treating a pathogenic infection in a subject, comprising administering a therapeutically effective amount of a p53 gene therapy to a subject infected or suspected of being infected by a pathogen.
The relative skill of those in the art: The relative skill of those in the art is high, with the majority of ordinary artisans possessing an advanced degree.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing for enablement, the claims are analyzed with respect to the teachings of the Specification and are to be “given their broadest reasonable interpretation consistent with the Specification.” See MPEP § 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the Examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
As such, the broadest reasonable interpretation of the instantly claimed method is that it provides a method for treating any pathogenic infection within a subject, comprising administering via any route a therapeutically effective amount that would need to be determined of a p53 gene therapy within any formulation to a subject infected or suspected of being infected by any pathogen. A skilled artisan would not know how to follow the method with a reasonable expectation of success based solely on what is disclosed in the Specification.
The amount of direction or guidance presented: The instant Specification recites mere embodiments of the method with limited applicability or guidance to the invention as claimed. For example, the instant disclosure states that an aspect of the invention is “methods of treating (e.g., suppressing or preventing) a pathogenic infection in a subject comprising administering to the subject an effective amount of a p53 gene therapy (Paragraph [0006] of instant Specification). The instant disclosure broadly defines the terms “treatment”, “therapeutic benefit”, and “effective amount”; however, this fails to provide specific details necessary to successfully perform the claimed method. See Paragraphs [0029]-[0032], [0098]-[0099], [0102], [0209]-[0210], [0225] of the instant Specification.
The presence or absence of working examples: The instant Specification provides few working examples; however, such examples are directed to 21 “antiviral/immune activation” genes that were upregulated or downregulated following intratumoral injection of an Ad-p53 virus, with said genes being linked to pathogenic infections. See Paragraphs [0273]-[0287] of the instant Specification. The Examiner notes that the fact such genes are correlated to pathogenic infections does not necessarily indicate that the modulation of such genes leads to the treatment of the pathogenic infections (i.e., correlation does not equal causation). There are no working examples that appear to comprise a method of treating a pathogenic infection within a subject, wherein the subject is administered a therapeutically effective amount of a p53 gene therapy.
More specifically in regards to the 21 genes listed within Table 1 of the disclosure, Applicant has supplied references supporting their assertion that the regulation of the particular gene results in the treatment of a pathogenic infection. The Examiner has reviewed at least one reference for those of record either on IDS filed 01 October 2024 or within Pages 98-104 of the instant Specification for each of the recited genes and found that support for association Applicant asserts is lacking for the following genes:
In regards to SOX2, the disclosure of Zhu et al, 2020 underscores the unpredictability of SOX2 and treating “pathogen infectivity”, as Zhu et al disclose that an increase in SOX2 expression results in a decrease in the antiviral response in Zika-infected cells. See Figures 2-4 of Zhu et al, 2020. These data support the opposite of Applicant’s assertion in Paragraph [00273] of the instant Specification, wherein p53 increases SOX2 expression, which allows for the treatment of pathogen infectivity.
In regards to S100A8 and S100A9, Voss et al disclose that S100A8 and S100A9 are upregulated within HSV-1 infected epidermal keratinocytes. See Page 198 of Voss et al. These data support the opposite of Applicant’s assertion in Paragraph [00274] of the instant Specification, wherein p53 increases S100A8 and S100A9 expression, which allows for the treatment of pathogen infectivity.
In regards to SERPINB5, Dzinic et al disclose the use of SEPRPINB5 in increasing the tumor cell antigenicity, as well as the correlation of SEPRINB5 expression with the activation and proliferation of a fraction of CD8+ T-cells in a certain subset of psoriatic patients. See Pages 3-4 of Dzinic et al. These data fail to support Applicant’s assertion in Paragraph [00275] of the instant Specification that the upregulation of SEPRINB5 via p53 allows for the treatment of a pathogenic infection.
In regards to CXCL8, CXCL9, CXCL10, CXCL11, CXCL13, and PRLR, the Examiner notes that the reference of Tamet et al, 2001 is not provided by Applicant within the IDS filed 01 October 2024 or Pages 98-104 of the instant Specification, and a search of the prior art does not readily provide this reference. Therefore, the Examiner cannot comment in regards to the listed genes.
In regards to ITGB8, Mair et al disclose that ECM changes during inflammation promoted a role for αv integrins in interstitial movement within the skin, thereby aiding in the clearance of infection. See Page 9 of Mair et al. However, Mair et al fail to disclose how the upregulation of ITGB8 influences the treatment of pathogen infectivity, as is asserted in Paragraph [0275] of the instant Specification.
In regards to PLA2G2A, Zhu et al, 2017 disclose that PLA2G2A serum levels are elevated in HBV patients and associated with disease progression, lymph node metastasis, and TNM stage. See Pages 4-5 of Zhu et al, 2017. However, Zhu et al fail to disclose how the downregulation of PLA2G2A influences the treatment of pathogen infectivity, which is also hindered by the uncertainty highlighted in Paragraphs [0276]-[0277] of the instant Specification in regulating PLA2G2A.
In regards to CD209, Yang et al disclose that THP-1 cells expressing full-length CD209 readily transfer SARS-CoV to Vero cells, indicating that CD209 or a related lectin on dendritic cells might facilitate cell-mediated transfer of the virus using the viral S protein. See Figure 3, Page 5647 of Yang et al. However, Yang et al fail to disclose how the downregulation of CD209 influences the treatment of pathogen infectivity, as is suggested in Paragraphs [0279]-[0280] of the instant Specification.
In regards to CCL18, Pardo et al disclose that an increase in CCL18 expression is associated with hypersensitivity pneumonitis. See Pages 610, 613-615 of Pardo et al. However, Yang et al fail to disclose how the downregulation of MARCO influences the treatment of pathogen infectivity, as is suggested in Paragraph [0283] of the instant Specification.
In regards to SFRP1, Selman et al disclose that an increase in SFRP1 expression is associated with idiopathic pulmonary fibrosis. See Table 1 of Selman et al. However, Selman et al fail to disclose how the downregulation of SFRP1 influences the treatment of pathogen infectivity, as is suggested in Paragraph [0284] of the instant Specification.
In regards to RELN, Baek et al disclose that a loss of RELN leads to profound defects in neuronal positioning and dendritogenesis in human and mouse, whereas ectopic expression in migrating neurons induces neuronal ectopia. See Page 6 of Baek et al. Baek et al fail to disclose how the downregulation of RELN influences the treatment of pathogen infectivity, as is suggested in Paragraph [0285] of the instant Specification.
In regards to IL1RN, Korthagen et al disclose that polymorphisms associated with the IL1RN gene variable number tandem repeat increase susceptibility to idiopathic pulmonary fibrosis, wherein the IL1RN risk allele is associated with lower levels of IL-1Ra mRNA expression. See Pages 371, 375-376 of Korthagen et al. However, Korthagen et al fail to disclose how the upregulation of IL1RN influences the treatment of pathogen infectivity, as is suggested in Paragraph [0286] of the instant Specification.
In regards to CCL14, LAMB3, and LAMC2, the Examiner notes that Applicant has failed to expand upon the relationship between p53 therapy and the treatment of a pathogenic infection when considering LAMB3 and LAMC2. Therefore, the Examiner cannot comment in regards to the listed genes.
Consequently, Applicant has not provided evidence of a working method that explicitly comprises the administration of a p53 gene therapy to a subject suffering from or suspected of suffering from a pathogenic infection.
The level of predictability in the art and quantity of experimentation necessary: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention.
Before the effective filing date of the claimed invention, the closest prior art to the instantly claimed invention is Nielsen et al (US 2001/0044420 A1). Nielsen et al disclose intratumoral administration of a nucleic acid encoding a p53 protein into the tumor mass of a subject suffering from cancer, wherein the administration of p53 reduces the tumorigenicity and malignancy of the affected cell mass (Paragraphs [0008], [0018], [0022]-[0023]). Therefore, the prior art teaches the administration of a p53 gene therapy into a subject suffering from cancer. The prior art does not disclose or otherwise suggest the treatment of a pathogenic infection.
It is also of note that the downstream effects of p53 are varied, and in some instances have opposite effects in vivo versus in vitro. See, for example, Page 1067 of Kastenhuber et al (Cell, 2017).
Therefore, a person having ordinary skill would have to perform further experimentation in order to perform the method commensurate in scope with the breadth of the claims.
Consequently, the instant Specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, to perform the claimed method without first making a substantial inventive contribution. Without explicit guidance in the disclosure as filed, a person having ordinary skill would have to perform further experimentation in order to successfully treat a pathogenic infection in a subject as broadly claimed. Given that the nature of the invention is the treatment of a pathogenic infection via the administration of a p53 gene therapy, and since the claims broadly encompass multiple pathogens, routes of administration, and p53 gene therapy formulations, undue further experimentation would be required in order to demonstrate the composition could be utilized with a reasonable expectation of success.
Thus, in view of the Wands factors, as discussed above, Applicant fails to provide information sufficient to perform claimed invention of a method of treating a pathogenic infection in a subject, comprising administering a therapeutically effective amount of a p53 gene therapy to a subject infected or suspected of being infected by a pathogen, as recited in instant claims 1-10, 13-16, 18-20, and 22-24.
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.
Claim 5 is 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.
Regarding claim 5: The instant claim recites the limitation "the p53 gene therapy composition" in Lines 1-2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a p53 gene therapy composition within the instant claim or parent claim 1. See MPEP § 2173.05(e).
Appropriate correction is required.
Claim Interpretation
A preamble is generally not accorded any patentable weight where it merely recites the purpose
of a process or the intended use of a structure or composition, and where the body of the claim does
not depend on the preamble for completeness but, instead, the process steps or structural limitations
are able to stand alone. See MPEP § 2111.02 (II) and In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976);
Kropa v. Robie, 88 USPQ 478, 481 (CCPA 1951). Therefore, the methods of the instant claims are
interpreted as being drawn to the specific structural limitations and process steps recited in the claims.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 41 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Nielsen et al (US 2001/0044420 A1, of record on IDS filed 01 October 2024).
Nielsen et al disclose the intratumoral administration of a nucleic acid encoding a p53 protein into the tumor mass of a subject suffering from cancer, wherein the administration of p53 reduces the tumorigenicity and malignancy of the affected cell mass (Paragraphs [0008], [0018], [0022]-[0023]).
Accordingly, Nielsen et al anticipate the claim as follows:
Regarding claim 41: Nielsen et al disclose the intratumoral administration of a nucleic acid
encoding a p53 protein into the tumor mass of a subject suffering from cancer, wherein the administration of p53 reduces the affected three-dimensional tumor cell mass. Given that the preamble of the instant method does not provide a structural limitation and instead recites an intended use – as is explained in the Claim Interpretation section above – and that Applicant has identified that the successful treatment of tumor stroma is an inherent result of the intratumoral administration of a p53 therapeutic – see Paragraphs [0019], [0031] of instant Specification – the intratumoral administration of a nucleic acid encoding a p53 protein as detailed in Nielsen et al will thereby also inherently treat the tumor stroma. This therefore reads on the method of the instant claim. See MPEP § 2112.02(I), (II).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633