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 .
For reissue applications filed on or after September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the current provisions.
Status of Application and Claims
US Patent 11,898,180 issued on 2/13/24 from underlying application 16/639,078 with claims 1-4. This reissue application was filed on 6/6/25 amending claims 1-4. Claims 1-4 are pending and under examination.
Specification
The substitute specification filed 6/6/25 fails to comply with 37 CFR 1.173(d) because the changes have not been made relative to the underlying ’180 patent. The substitute specification appears to demonstrate changes relative to the specification filed in the underlying ’078 application, but this is improper. 37 CFR 1.173(d) specifically refers to markings showing “changes made relative to the patent being reissued.”
Furthermore, applicant must identify the column and line number within the underlying ’180 patent for each change being made. For example, the examiner notes an attempt to delete the phrase “of the invention” in the heading between paragraphs 10 and 11 in the unpaginated substitute specification and to replace words at paragraph 12 of that document. Instead of marking up in this way, applicant must provide the location of each change and give instructions for the desired change. MPEP 1453(I) is instructive:
All amendments submitted under 37 CFR 1.173(b)(1)(i), which include any deletions or additions, must be made by submission of the entire text of each added or rewritten paragraph with markings (single brackets and underlining), except that an entire paragraph of specification text may be deleted by a statement deleting the paragraph without presentation of the text of the paragraph. Applicant must indicate the precise point where any added or rewritten paragraph is located.
There is no provision in reissue practice for a marked-up substitute specification. All changes must be made in accordance with 37 CFR 1.173(b) and (d).
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 1-4 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 1 is drawn to a method of selectively inhibiting a cancer cell with low asparagine synthetase (ASNS) expression by introducing first an arginase, then an asparaginase, to the cell’s media to reduce arginine and asparagine concentrations, respectively. Claim 1 requires that the enzymes “provide a synergistic effect in reducing viability of the cancer cell” that “exceeds additive effects of monotherapies” in the low-ASNS-expressing cells with either enzyme alone. The as-filed disclosure does not demonstrate to skilled artisans that applicants possessed such a method.
Before the effective filing date of the claimed invention, skilled artisans recognized a subset of cancer cells with relatively low ASNS expression. Lubin et al. (US 20120094947; reference A) teaches, “Many acute lymphoblastic leukemias [ALLs] (as well as some other leukemias, malignant melanomas, T-cell lymphomas, multiple myelomas, and ovarian cancers) are known to be deficient in the enzyme asparagine synthase, and these tumors depend on an exogenous supply of asparagine.” (Paragraph 189.) Lubin teaches that treating these tumors with asparaginase (ASNase) to deplete asparagine levels was likewise known. (Paragraph 189.) Su and Pan (2008, Pediatric Blood Cancer 50: 274-279; NPL reference 27 on 6/6/25 IDS) teach ASNase is an important chemotherapeutic for childhood acute lymphoblastic leukemia (ALL) and that clinical trials have shown that intensified ASNase treatment can improve outcomes. (Page 274, column 1.) See also Moscow et al. (2014, US Patent 8663632; reference B) at column 19, lines 43-49 (describing the biology and the treatment methods).
Regarding arginine, however, skilled artisans recognized the usefulness of administering inhibitors of arginase to treat cancers including ALL by increasing arginine levels. See Gross et al. (US 20160375044; reference C) at abstract and paragraphs 278-279. Gross explains that arginine is important for the activation, growth, and survival of a body's cancer-fighting cytotoxic T-cells. (Paragraph 3.) Gross teaches that depletion of arginine due to elevated levels of arginase has been observed in renal cell carcinoma and acute myeloid leukemia. (Paragraph 276.)
Given the teachings of Lubin, Su, and Moscow that asparagine levels are high in ALL and Gross’s teaching that arginine levels are low in ALL, the skilled artisan would not have predicted that providing arginase to deplete arginine levels would have improved the ability of asparaginase to reduce asparagine levels, thereby treating ALL. The field of inhibiting low-ASNS-expressing cancer cells by depleting both arginine and asparagine was therefore unpredictable. See MPEP 2163(II)(A)(3)(a)(i) (“Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.”) For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession than is required in mature technologies. See MPEP 2163(II)(A)(3)(a)(i).
Applicants provide a single relevant working example in which combinations of arginase and asparaginase were added in various amounts and ratios to cultures of several cancer-cell lines. (Columns 17-19.) Specifically, applicants added ASNase alone to the media of both low- and high-ASNS-expressing cancer-cell lines in amounts from 0.016-2 units per mL of media. (Figure 17.) Applicants observed around 70-80% viability in low-ASNS-expressing cancer-cell lines with 2U/mL ASNase. (Figure 17, box (i).) Applicants write, “Inventors have found that deprivation of asparagine alone provides little inhibitory effect on cancer cells.” (Column 19, lines 8-9.) This finding, however, contradicts the long-held understanding in the art that ASNase treatment is standard for treating ALL, a low-ASNS-expressing cancer.
It appears that applicant has identified some ASNase levels that do not, on their own, inhibit the growth of certain low-ASNS-expressing cancer cells and then observed that adding arginase (rhArg) to ASNase at those levels improves cell killing in those specific low-ASNS-expressing cancer cells. (See Figure 18, box (i), and Table 5 at columns 18-19.) The claims, however, are not limited to any particular amounts of arginase or asparaginase or to any particular low-ASNS-expressing cancer cells. The skilled artisan regarding the disclosure would have predicted based on Lubin, Su, and Moscow that adding ASNase to the media of low-ASNS-expressing cancer cells would result in reduced cell viability. As such, the skilled artisan would not have considered the as-filed disclosure as showing possession of a synergistic treatment at all ASNase concentrations. The written-description requirement has therefore not been met for claim 1. Claims 2-4 depend from claim 1 and do not rectify the issue of possession, so they must also be rejected under 35 U.S.C. 112(a).
Claim Rejections—35 U.S.C. 251
Claims 1-4 are rejected under 35 U.S.C. 251 as failing to satisfy the reissue standard of 35 U.S.C. § 251, specifically the requirement that the reissued patent claim the invention disclosed in the original patent.
Under the original patent requirement, “it is not enough that an invention might have been claimed in the original patent because it was suggested or indicated in the specification.” U.S. Indus. Chemicals, Inc. v. Carbide & Carbon Chemicals Corp., 315 U.S. 668, 676 (1942). “Rather, the specification must clearly and unequivocally disclose the newly claimed invention as a separate invention.” Antares Pharma, Inc. v. Medac Pharma Inc., 771 F.3d 1354, 1362 (Fed. Cir. 2014) (citing Industrial Chemicals, 315 U.S. at 676). Furthermore:
The ‘original patent’ standard and the written description requirement are not the same. Where the written description requirement is based on what the skilled artisan would have understood was within the possession of the inventor, recent Federal Circuit case law indicates that the original patent requirement under § 251 requires something more.
MPEP 1412.01(I) (quoting Ex parte Sandwick, Appeal No. 2018-008369, op. at 22 (PTAB July 23, 2019)).
The claimed invention does not find written-description support in the underlying patent, so it cannot have been clearly and unequivocally disclosed in the underlying patent as a separate invention. As such, the original patent requirement has not been met.
Conclusion
No claims are allowed.
Maintenance Fees
Applicant is reminded of the requirement to pay all applicable maintenance fees on the original patent. See MPEP 1415.01.
Duty to Disclose
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which Patent No. 11,898,180 is or was involved. These proceedings would include any trial before the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lora E Barnhart Driscoll, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached at 571-272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Lora E Barnhart Driscoll/ Patent Reexamination Specialist, Art Unit 3991
Conferees:
/KSO/
Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/ SPRS, Art Unit 3991
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