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 .
Detailed Action
This action is in response to the papers filed October 15, 2025.
Amendments
Applicant's amendments, filed October 15, 2025, is acknowledged. Applicant has cancelled Claims 1-16, and amended Claims 18, 25, and 29.
Claims 17-33 are pending.
Election/Restrictions
Applicant has elected with traverse the invention of Group I, Claim(s) 17-28 and 32, drawn to an engineered immune cell defective for SOCS-1, and a method of using said cell in an adoptive cellular therapy for the treatment of cancer.
Within Group I, Applicant has elected without traverse the following species, wherein:
i) the alternative additional genetic modification is FAS, as recited in Claims 18 and 24; and
ii) the alternative agent to inhibit the expression and/or activity of the target molecule(s) is gene editing, as recited in Claim 31.
Response to Arguments
Applicant argues that Group II is directed to making the product of Group I, which, in light of Applicant’s species election of FAS, the Examiner finds persuasive.
Claims 17-33 are pending.
Claims 19, 25, and 27-28 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 17-18, 20-24, 26, and 29-33 are under consideration.
Priority
This application is a 371 of PCT/EP2021/71504 filed on July 30,2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d). A certified copy of EPO 20305878.9 filed on July 30, 2020 is filed with the instant application.
Information Disclosure Statement
Applicant has filed Information Disclosure Statements on January 30, 2023 and September 15, 2025 that has been considered.
The information disclosure statement filed September 15, 2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
NPL citations have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
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
1. The prior objection to Claims 18, 25, and 29 is withdrawn in light of Applicant’s amendments to the claims.
2. Claims 18, 24, and 29-30 are objected to because of the following informalities:
Claim 17 recites “SOCS-1”.
Claims 18, 24, and 29-30 recite “SOCS1”.
Applicant should be consistent with their lexicography. Choose one, but not both.
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.
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.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
3. Claim(s) 18 and 29-31 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, Claim 18 recites the broad recitation “further defective for at least one additional protein”, and the claim also recites “particularly…” and “optionally…” which is/are the narrower statement of the range/limitation.
Claim 29 recites the broad recitation “inhibiting the express…”, and the claim also recites “optionally…” which is/are the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The terms “particularly” and “optionally” are exemplary language and render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
4. Claim(s) 29-31 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 29 recites a method of producing a universal genetically engineered immune cell comprising the step of inhibiting the expression and/or activity of SOCS1 and/or FAS.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
The term “universal” is a relative term which renders the claim indefinite. The term “universal” 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.
Compare/contrast the genetically engineered immune cells of Claims 17 and 32, and instant Claim 29.
Either the cells of Claims 17 and 32 inherently possess the functional property of being “universal”, per natural law of cell biology, or they do not, and something must change.
To the extent the cells of Claims 17 and 32 do not inherently possess the functional property of being “universal”, then instant Claim 29 is considered indefinite for failing to recite the structure(s) and/or method step(s) that is/are necessary and sufficient to cause the recited functional language “universal”.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
In the instant case, the limitation “universal” merely states a functional characteristic without providing any indication about how the functional characteristic is provided. The functional characteristic does not follow from (is not an inherent property of) the structure recited in the claim, so it is unclear whether the claim requires some other structure to be added to the composition to provide the functional characteristic.
While it is clear, for example, that the claim requires the step of inhibiting the expression and/or activity of SOCS1, the specification fails to disclose whether or not that this single step renders the modified immune cell to be “universal”. Thus, the claim is considered to be incomplete for omitting essential step(s), such omission amounting to a gap between the steps and/or omitting essential structural cooperative relationships of elements. See MPEP § 2172.01.
Similarly, while it is clear, for example, that the claim requires the step of inhibiting the expression and/or activity of FAS, the specification fails to disclose whether or not that this single step renders the modified immune cell to be “universal”. Thus, the claim is considered to be incomplete for omitting essential step(s), such omission amounting to a gap between the steps and/or omitting essential structural cooperative relationships of elements. See MPEP § 2172.01.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
When functional claim language is found indefinite, it typically lacks an adequate written description under §112(a), because an indefinite, unbounded functional limitation would cover a plurality of undisclosed structures and/or method steps of performing a function and indicate that the inventor has not provided sufficient disclosure to show possession of the invention. Thus, in most cases, a §112(b) rejection that is based on functional language having unclear (or no) claim boundaries should be accompanied by a rejection under §112(a) based on failure to provide a written description for the claim. See MPEP 2173.05(g).
5. Claim(s) 29-31 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 29 recites a method of producing a universal genetically engineered immune cell comprising the step of inhibiting the expression and/or activity of SOCS1 and/or FAS.
Compare/contrast the genetically engineered immune cells of Claims 17 and 32, and instant Claim 29.
Either the cells of Claims 17 and 32 inherently possess the functional property of being “universal”, per natural law of cell biology, or they do not, and something must change.
To the extent the cells of Claims 17 and 32 do not inherently possess the functional property of being “universal”, then instant Claim 29 is considered to lack adequate written description for failing to recite the structure(s) and/or method step(s) that is/are necessary and sufficient to cause the recited functional language “universal”.
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).
In the instant case, the limitation “universal” merely states a functional characteristic without providing any indication about how the functional characteristic is provided. The functional characteristic does not follow from (is not an inherent property of) the structure recited in the claim, so it is unclear whether the claim requires some other structure to be added to the composition to provide the functional characteristic.
The term “universal” 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.
While it is clear, for example, that the claim requires the step of inhibiting the expression and/or activity of SOCS1, the specification fails to disclose whether or not that this single step renders the modified immune cell to be “universal”. Thus, the claim is considered to be incomplete for omitting essential step(s), such omission amounting to a gap between the steps and/or omitting essential structural cooperative relationships of elements. See MPEP § 2172.01.
Similarly, while it is clear, for example, that the claim requires the step of inhibiting the expression and/or activity of FAS, the specification fails to disclose whether or not that this single step renders the modified immune cell to be “universal”. Thus, the claim is considered to be incomplete for omitting essential step(s), such omission amounting to a gap between the steps and/or omitting essential structural cooperative relationships of elements. See MPEP § 2172.01.
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)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
6. Claim 26 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.
Claim 26 recites the limitation "wherein the target antigen" in reference to the engineered immune cell of Claim 17. There is insufficient antecedent basis for this limitation in the claim because Claim 17 fails to recite a ‘target antigen’.
Rather, it appears Claim 26 has suffered a typographical error, and should instead be dependent upon Claim 19.
7. Claim(s) 33 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.
The phrase “which is for” is exemplary language and render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The phrase “which is for allogenic cellular therapy” is an intended use limitation, which does not contain any further structural limitations with respect to claimed method of the independent claim. See MPEP §2114).
Applicant should amend the claim to recite, e.g., ‘wherein the adoptive cellular therapy is allogenic cellular therapy’, for example.
8. Claim 30 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.
The term “agent inhibiting the expression and/or activity…and/or disrupting the….gene” in Claim 30 is a relative term which renders the claim indefinite.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, Claim 30 recites the broad recitation “agent inhibiting the expression and/or activity…and/or disrupting the….gene”, and the claim also recites “disrupting the….gene” which is/are the narrower statement of the range/limitation.
As evidenced by Claim 31, the “agent inhibiting the expression and/or activity” is a gene editing agent, which is recognized by those of ordinary skill in the art to fulfill “disrupting the….gene”.
Thus, Claim 30 appears to be internally redundant.
9. Claim 30 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 29 recites a method of inhibiting the expression and/or activity of SOCS1 and/or FAS in an immune cell.
Claim 30 recites the method comprises the step of contacting the immune cell with an agent that inhibits the expression and/or activity of SOCS1 and/or FAS.
Such fails to further limit the independent claim because it is axiomatic that in order to perform the method of the independent claim, one must necessarily contact the immune cell with said agent, as recited in the dependent claim
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
10. Claims 22-23 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The recitation of a process limitation in Claims 22-23 is not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 22-23 imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the engineered immune cell defective for SOCS1 were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
11. Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 recites wherein the immune cell is isolated from a subject.
Claim 23 recites wherein the subject has, or is at risk of having, cancer.
Claim 23 fails to further limit Claim 22 because those of ordinary skill in the art immediately recognize that there are only two options, per natural law of biology, that the subject has, or is at risk of having, cancer, and thus reciting both options is not further limiting.
Furthermore, everyone is at risk of having cancer, per natural law of biology.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
12. Claim(s) 17, 20-24, and 29-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hildebrand et al (Frontiers in Immunology 10: e1279, 12 pages, doi: 10.3389/fimmu.2019.01279; available online June 3, 2019; of record).
With respect to Claim 17, Hildebrand et al is considered relevant prior art for having taught an engineered immune cell, e.g. monocytes, expressing a SOCS1 siRNA, thereby inhibiting the expression and/or activity of SOCS1 in said engineered immune cell (e.g. pg 5, col. 1, siRNA-mediated knockdown of SOCS1).
With respective to Claim 24, Hildebrand et al taught expressing a SOCS1 siRNA, thereby inhibiting the expression and/or activity of SOCS1 in said engineered immune cell (e.g. pg 5, col. 1, siRNA-mediated knockdown of SOCS1).
With respect to Claims 22-23, Hildebrand et al taught isolating primary immune cells from a subject (e.g. pg 3, col. 1, Methods).
Furthermore, as discussed above, instant claims fail to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections above.
With respect to Claims 20-21, Hildebrand et al taught isolating primary immune cells comprising CD4+ and CD8+ T cells (e.g. pg 3, col. 1, Methods).
With respect to Claims 29-30, Hildebrand et al taught a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of SOCS1 (e.g. pg 5, col. 1, siRNA-mediated knockdown of SOCS1).
Hildebrand et al performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of SOCS1 are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Hildebrand et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
Thus, Hildebrand et al anticipate the claims.
13. Claim(s) 17, 20-24, and 29-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shifrut et al (Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function, Cell 175: 1958-1971, December 13, 2018; of record in specification).
With respect to Claim 17, Shifrut et al is considered relevant prior art for having taught an engineered immune cell, e.g. T cells, genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
With respective to Claim 24, Shifrut et al taught an engineered immune cell, e.g. T cells, the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
With respect to Claims 22-23, Shifrut et al taught isolating primary immune cells from a subject (e.g. Figure 1a).
Furthermore, as discussed above, instant claims fail to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections above.
With respect to Claims 20-21, Shifrut et al taught isolating primary immune cells comprising CD8+ T cells (e.g. Supplemental Methods).
With respect to Claims 29-31, Shifrut et al taught a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of SOCS1, to wit, the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
Shifrut et al performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of SOCS1 are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Shifrut et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
Thus, Shifrut et al anticipate the claims.
14. Claim(s) 29-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dotti et al (Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis, Blood 105(12): 4677-4684, 2005).
With respect to Claims 29-30, Dotti et al is considered relevant prior art for having taught a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of Fas, to wit, siRNA (e.g. pg 4680, col. 1, “siRNA-mediated knockdown of Fas in…CTLs”).
Dotti et al performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of Fas are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Dotti et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
Thus, Dotti et al anticipate the claims.
15. Claim(s) 29-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ren et al (A versatile system for rapid multiplex genome-edited CAR T cells, Oncotarget 8(10): 17002-17011, 2017; of record in IDS).
With respect to Claims 29-31, Ren et al is considered relevant prior art for having disclosed a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of Fas (syn. CD95), to wit, CRISPR/Cas9 gene editing system (e.g. pg 17004-17005).
Basar et al performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of Fas (syn. CD95) are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Ren et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
Thus, Ren et al anticipate the claims.
16. Claim(s) 29-31 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Basar et al (U.S. 2022/0031749; priority to November 28, 2018).
With respect to Claims 29-31, Basar et al is considered relevant prior art for having disclosed a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of Fas (syn. CD95), to wit, CRISPR/Cas9 gene editing system (e.g. [0005, 9, 98]; Table 1; claims 1 and 15).
Basar et al performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of Fas (syn. CD95) are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Basar et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
Thus, Basar et al anticipate the claims.
Claim Rejections - 35 USC § 103
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 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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
17. Claims 17, 20-24, and 29-33 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Shifrut et al (Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function, Cell 175: 1958-1971, December 13, 2018; of record in specification), as applied to Claims 17, 20-24, and 29-31 above, and in further view of Marson et al (WO 2020/014235; filed July 9, 2019; co-authors to Shifrut et al; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 17, Shifrut et al is considered relevant prior art for having taught an engineered immune cell, e.g. T cells, genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
Shifrut et al do not teach a method of treating cancer comprising the step of administering to a subject immune cells genetically engineered to inhibit expression and/or activity of SOCS1.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 32, Marson et al is considered relevant prior art for having disclosed an engineered immune cell, e.g. T cells, genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. [0113], CRISPR-ablation of SOCS1), wherein said genetically engineered T cells are used in a method of treating cancer in a subject (e.g. Abstract; [0010]). Marson et al disclosed wherein the T cells are obtained from a subject that has cancer, are genetically modified, and then reintroduced into the subject (syn. autologous) [0083].
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, and gene silencing and/or gene editing techniques. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to arrive at a method of treating cancer in a subject comprising the step of administering to said subject at least one immune cell genetically engineered to inhibit the expression and/or activity of SOCS1 with a reasonable expectation of success because those of ordinary skill in the art previously recognized the scientific and technical concepts that:
i) SOCS1 expression and/or activity behaves as a negative regulator of T cell function, being an art-recognized T cell inhibitory gene (Shifrut et al; Marson et al);
ii) T cells genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene had been successfully reduced to practice (Shifrut et al; Marson et al); and
iii) Marson et al disclosed said T cells genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene may be used in methods of treating cancer in a subject, whereby the patient’s own T cells are genetically modified and then reintroduced back into the patient (e.g. [0083]), as inactivation of the negative regulator boosts T cell function (e.g. [0105]), e.g. significantly increased tumor cell clearance (e.g. [0113]).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respective to Claim 24, Shifrut et al taught an engineered immune cell, e.g. T cells, the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
Marson et al disclosed an engineered immune cell, e.g. T cells, the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
With respect to Claims 22-23, Shifrut et al taught isolating primary immune cells from a subject (e.g. Figure 1a).
Marson et al disclosed wherein the T cells are obtained from a subject that has cancer, are genetically modified, and then reintroduced into the subject (syn. autologous) [0083].
Furthermore, as discussed above, instant claims fail to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections above.
With respect to Claims 20-21, Shifrut et al taught isolating primary immune cells comprising CD8+ T cells (e.g. Supplemental Methods).
Marson et al disclosed isolating primary immune cells comprising CD8+ T cells [0123].
With respect to Claims 29-31, Shifrut et al taught a method of producing a universal genetically engineered immune cell, the method comprising the step of contacting the immune cell with an agent that inhibits the expression and/or activity of SOCS1, to wit, the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. pg 1966, col. 1, “CRISPR-ablation of…SOCS1”).
Marson et al disclosed an engineered immune cell, e.g. T cells, genetically modified using the CRISPR/Cas9 gene editing system to disrupt the SOCS1 gene (e.g. [0113], CRISPR-ablation of SOCS1), wherein said genetically engineered T cells are used in a method of treating cancer in a subject (e.g. Abstract; [0010]).
Shifrut et al and Marson et al each performed the positively recited method step(s), and thus said immune cells genetically modified to inhibit expression and/or activity of SOCS1 are considered to be “universal”.
To the extent Applicant argues the genetically modified immune cells of Shifrut et al and/or Marson et al are not “universal”, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections above.
With respect to Claim 33, Marson et al disclosed wherein the T cells are obtained from a subject that has cancer, are genetically modified, and then reintroduced into the subject (syn. autologous) [0083].
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
18. Claims 18, 24, and 29-33 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Shifrut et al (Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function, Cell 175: 1958-1971, December 13, 2018; of record in specification) and Marson et al (WO 2020/014235; filed July 9, 2019; co-authors to Shifrut et al; of record in IDS), as applied to Claims 17, 20-24, and 29-33 above, and in further view of Ren et al (a versatile system for rapid multiplex genome-edited CAR T cells, Oncotarget 8(10): 17002-17011, 2017; of record in IDS) and Frost et al (U.S. 2017/0356010).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Shifrut et al nor Marson et al teach/disclose wherein the immune cells genetically engineered to inhibit expression and/or activity of SOCS1 are further engineered to inhibit expression and/or activity of Fas (syn. CD95).
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 18, 29-30, and 32, Ren et al is considered relevant prior art for having taught an immune cell genetically engineered to inhibit expression and/or activity of Fas, alone (e.g. pg 17004-17005) and/or with inhibiting the expression of PD1 and CTLA-4, thereby resulting in an inhibitory pathway-resistant universal T cell (e.g. pg 17003, col. 1). Ren et al taught a xenograft animal cancer model system, wherein the genetically modified T cells are administered to the mouse animal subject (e.g. pg 17009, col. 1, Methods, Mouse xenograft studies).
Ren et al taught that those of ordinary skill in the art previously recognized that ablating Fas (syn. CD95) would lead to an enhancement in T cell function (e.g. pg 17003, col. 1). Ren et al taught that the Fas-negative T cells exhibited a reduction of apoptosis when repeatedly challenged with target cells, leading to increased T cell expansion and reduced activation-induced cell death (AICD) (e.g. pg 17004, col. 2).
Frost et al is considered relevant prior art for having disclosed immune cells genetically modified to inhibit expression and/or activity of SOCS1 and PD1 (e.g. [0009, 199, 502, 572]). Frost et al disclosed wherein inhibition of SOCS1 and PD1 expression and/or activity is lymphproliferative to induce proliferation of the T cells (e.g. [0188], lymphoproliferative element; [0199]; [0121], as SOCS1 is an art-recognized negative regulator of T cell activation [0201] and PD1 is recognized in the art to function to prevent activation of T cells [0205], and the inhibition of SOCS1 and/or PD1 expression and/or activity prevents T cell inactivation [0121].
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to modify the immune cells of Shifrut et al and/or Marson et al comprising a genetic modification that inhibits the expression and/or activity of SOCS1 to further comprise a genetic modification that inhibits the expression and/or activity of Fas (syn. CD95) with a reasonable expectation of success and motivation because:
i) Ren et al taught an immune cell genetically engineered to inhibit expression and/or activity of Fas, alone and/or with inhibiting the expression of PD1, thereby resulting in an inhibitory pathway-resistant universal T cell, whereby those of ordinary skill in the art previously recognized that ablating Fas (syn. CD95) would lead to an enhancement in T cell function, and that the Fas-negative T cells exhibited a reduction of apoptosis when repeatedly challenged with target cells, leading to increased T cell expansion and reduced activation-induced cell death (AICD); and
ii) Frost et al disclosed immune cells genetically modified to inhibit expression and/or activity of SOCS1 and PD1, whereby inhibition of SOCS1 and PD1 expression and/or activity is lymphproliferative to induce proliferation of the T cells, as SOCS1 is an art-recognized negative regulator of T cell activation and PD1 i