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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/6/2025 has been entered.
Response to Amendment
The amendment filed 6/6/2025, amending claims 1, 3, 6-8, 15-17, and 22 and cancelling claims 2, 4, 5, 19-21, and 26-34 is acknowledged. Claim 22 is pending and under examination. Applicant’s amendments to the claims have overcome each and every objection, 112(a) rejection, 102, 103, and double patenting rejection previously set forth in the Final Office Action mailed 2/6/2025.
The amendment to the claims filed on 6/6/2025 does not comply with the requirements of 37 CFR 1.121(c). Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
The correct status identifier for claims 15-17 is (Withdrawn- Currently Amended).
Allowable Subject Matter
The prior indication of claim 22 is withdrawn in light of an updated search identifying new prior art necessitating new grounds of rejection set forth below. Rejections based on the newly cited reference(s) follow.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 22 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed cell composition is directed to a natural product.
Applicant arguments are addressed at the end of the Office Action.
Broadest Reasonable Interpretation of Claim 22
Claim 22 recites:
A Treg cell comprising: a genetic modification or heterologous polynucleotide that inhibits expression of Rnf20
Claim 22 is directed to a Treg cell with inhibited Rnf20 expression.
As recited in claim 22, the claimed Treg cell encompasses a genus of naturally occurring cells, including human Treg cells that naturally comprise a deletion that removes an Rnf20 allele. Additionally, the claimed Treg cell encompasses Tregs obtained from RNF20 knockout mice and RNF20+/- mice.
As recited in claim 22, no structural characteristics of the cells are identified.
The claimed cell population is described by function only (i.e., gene inhibited) and cells having that function are taught in the art for the same purpose. The claimed genus of Treg cells embraces naturally occurring Treg cells with a genetic modification that reduces Rnf20 expression, as disclosed by Dugan (Dugan, Sarah L., et al. "Delineation of the 9q31 deletion syndrome: Genomic microarray characterization of two patients with overlapping deletions." American Journal of Medical Genetics Part A 176.12 (2018): 2901-2906.) for example.
Dugan discloses patients with 9q31 deletions, including 9q31.1q31.1 (Abstract; pg. 2901, col 2, para 1; Fig. 2). As evidenced by OMIM, an online catalog of human genes and genetic disorders, the cytogenetic location of Rnf20 is 9q31.1 (see attached OMIM Rnf20 deletion). Therefore, the cell of the claimed invention does not differ from a naturally occurring cell.
Tarcic (Tarcic, Ohad, et al. "RNF20 links histone H2B ubiquitylation with inflammation and inflammation-associated cancer." Cell reports 14.6 (2016): 1462-1476.) discloses that colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, and that Rnf20 is reduced in many cancers (Abstract; pg. 1464, col 1, para 2). Additionally, colons of UC patients tend to under express RNF20 mRNA (pg. 1464, col 1, para 3). Since RNF20 is naturally downregulated in the cells of ulcerative colitis patients and in colorectal tumors, and considering the variability in levels of downregulation of a gene that may naturally occur, the cell of the claimed invention read on the naturally occurring patient cells disclosed by Tarcic.
Guppy (Guppy, Brent J., and Kirk J. McManus. "Synthetic lethal targeting of RNF20 through PARP1 silencing and inhibition." Cellular Oncology 40.3 (2017): 281-292.) discloses
that RNF20 has been found to be somatically mutated or deleted in a number of cancer types, including colon, breast, lung and prostate cancer (pg. 282, col 2, para 2; Table 1). Therefore, the cell of the claimed invention does not differ from a naturally occurring cell as disclosed by Guppy.
Under Step 1 of the subject matter eligibility test for products and processes, it
must be determined if the claim is to a process, machine, manufacture or a composition
of matter. In the instant case, claim 22 is directed to a composition of matter (i.e., a Treg cell). The claim is therefore directed to a statutory category, a product.
Under Revised Step 2A, prong 2 of the analysis (determining the Judicial
Exceptions), it must be determined if the claim is directed to a law of nature, a natural
phenomenon (product of nature) or an abstract idea. In the instant case, the cell
is a naturally occurring product (a Treg cell with inhibited Rnf20 expression due to a naturally occurring genetic modification), disclosed by Dugan, Tarcic, and Guppy as being the same formulation as found in nature. Because the composition is the same as a product of nature, it falls within a judicial exception.
Under Step 2A, prong 2 of the analysis, it must be determined whether the claim
recites additional elements that amount to significantly more than the judicial exception.
In the instant case, the claim fails to recite any additional elements that integrate the
judicial exception (Treg cell with inhibited Rnf20 expression due to a naturally occurring genetic modification) into a practical application, and therefore the claim remains directed to a judicial exception invoking further analysis under step 2B.
Under Step 2B, it must be determined if the claim recites additional elements that
amount to significantly more than the judicial exception. In the instant case, claim 22
fails to recite any additional elements that amount to significantly more than the judicial
exception. Therefore, the claim as a whole does not amount to significantly more than
the exception itself (there is no inventive concept in the claim) and is not eligible, thus
concluding the eligibility analysis.
Claim Rejections - 35 USC § 112(a)
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.
Claim 22 is 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.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
Claim 22 is broad for reciting a genus of structures that have the functional property of inhibiting expression of Rnf20, which reasonably encompasses any Treg cell comprising any heterologous nucleic acid and/or any genetic modification (including those that are naturally occurring) that results in inhibition of Rnf20, either directly or indirectly.
Disclosure of putative structures having a theorized function in the absence of experimental data demonstrating the theorized function is insufficient to demonstrate possession of a representative number of species by disclosure of relevant, identifying characteristics (i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics), sufficient to show the applicant was in possession of the claimed invention.
Possession has not been demonstrated for the enormously vast genus of undisclosed structures that necessarily and predictably possess the functional property of inhibiting expression of Rnf20. Guidance in the specification includes:
[0007] In some embodiments, the inhibiting in a Treg cell comprises contacting a polynucleotide encoding the protein with a targeted nuclease, a guide RNA (gRNA), an siRNA, an antisense RNA, microRNA (miRNA), or short hairpin RNA (shRNA). In some embodiments, the inhibiting comprises contacting the polynucleotide encoding the nuclear factor with at least one gRNA and optionally a targeted nuclease, wherein the at least one gRNA comprises a sequence selected from Table 3. In some embodiments, the inhibiting comprises mutating the polynucleotide encoding the protein. In some embodiments, the inhibiting comprises contacting the polynucleotide with a targeted nuclease.
[0008] In some embodiments, the targeted nuclease introduces a double-stranded break in a target region in the polynucleotide. In some embodiments, the targeted nuclease is an RNA- guided nuclease. In some embodiments, the RNA-guided nuclease is a Cpfl nuclease or a Cas9 nuclease and the method further comprises introducing into a Treg cell a gRNA that specifically hybridizes to a target region in the polynucleotide. In some embodiments, the Cpfl nuclease or the Cas9 nuclease and the gRNA are introduced into the Treg cell as a ribonucleoprotein (RNP) complex. In some embodiments, the inhibiting comprises performing clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome editing.
Additionally, [0070-0100] provides general information on genome editing methods such as CRISPR/Cas, Zinc-finger nucleases, TALENs, meganucleases, and various RNA-based technologies, all of which may be used to inhibit Rnf20 in the claimed invention.
Further, [0123-0124] generically recites using CRISPR-Cas9 RNP to knock out candidate genes such as Rnf20 in Tregs.
While the specification includes some methods of genetic modification, it does not offer further guidance on the metes and bounds of the structure of a Treg cell comprising a genetic modification or heterologous polynucleotide that inhibits expression of Rnf20, directly or indirectly.
The claims fail to recite, and the specification fails to disclose, the structure/function nexus of the vast genus of structures that have the functional property of inhibiting Rnf20 expression.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. These claims are usually handled in Technology Center 1600. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id. The Amgen decision will be added to the MPEP in due course.
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”).
Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)
The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 “merely by clearly describing one embodiment of the thing claimed.” LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005).
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are “representative of the full variety or scope of the genus,” or by the establishment of “a reasonable structure-function correlation.” Such correlations may be established “by the inventor as described in the specification,” or they may be “known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014)
In Amgen, Inc., v. Sanofi (872 F.3d 1367 (2017)
At 1375, [T]he use of post-priority-date evidence to show that a patent does not disclose a representative number of species of a claimed genus is proper.
At 1377, [W]e questioned the propriety of the "newly characterized antigen" test and concluded that instead of "analogizing the antibody-antigen relationship to a `key in a lock,'" it was more apt to analogize it to a lock and "a ring with a million keys on it." Id. at 1352.
An adequate written description must contain enough information about the actual makeup of the claimed products — "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," which may be present in "functional" terminology "when the art has established a correlation between structure and function." Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-
16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid on PCSK9 ... does not tell you anything at all about the structure of the antibody"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody-antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In the instant case, knowing that the structure has the function of inhibiting Rnf20 expression does not tell you anything at all about the structure of the enormously vast genus of Treg cells (and genetic modifications/heterologous polynucleotides).
In Amgen, Inc., v. Sanofi (U.S. Supreme Court, No. 21-757 (2023))
“Amgen seeks to monopolize an entire class of things defined by their function”.
“The record reflects that this class of antibodies does not include just the 26 that Amgen has described by their amino acid sequence, but a “vast” number of additional antibodies that it has not.”
“It freely admits that it seeks to claim for itself an entire universe of antibodies.”
In the instant case, the record reflects that the claimed class of structures having the function of inhibiting Rnf20 is an enormously vast genus of undisclosed structures that is recited at a high level of generality, and encompasses direct (e.g., CRISPR, siRNA, KO) means and indirect means of inhibition.
“They leave a scientist forced to engage in painstaking experimentation to see what works. 159 U.S., at 475.
This is not enablement. More nearly, it is “a hunting license”. Brenner v. Manson, 383 U.S. 519, 536 (1966).
“Amgen has failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation”.
While the “roadmap” would produce functional combinations, it would not enable others to make and use the functional combinations; it would instead leave them to “random trial-and-error discovery”.
“Amgen offers persons skilled in the art little more than advice to engage in “trial and error”.
“The more a party claims for itself the more it must enable.”
“Section 112 of the Patent Act reflects Congress’s judg-ment that if an inventor claims a lot, but enables only a lit-tle, the public does not receive its benefit of the bargain. For more than 150 years, this Court has enforced the stat-utory enablement requirement according to its terms. If the Court had not done so in Incandescent Lamp, it might have been writing decisions like Holland Furniture in the dark. Today’s case may involve a new technology, but the legal principle is the same.
Accordingly, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the enormously vast genus of structures having the function of inhibiting expression of Rnf20.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638