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
Priority to US 63/230,225, filed 8/6/2021, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 10/12/2022, 7/18/2024, and 1/3/2025, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, and 97-99 are pending in the application. Claims 2, 3, 5, 12, 15, 16, 65-67, 69-73, 75-77, 81, 82, 85-88, 91, and 94-96 are canceled. Claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, and 97-99 are currently under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 14-16, and 19, 32, 36, 38, 39, 41, 44, 45, 48, 53, 54, and 56-57 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant Reply, filed 10/20/2025, page 7, para. 2, with respect to claims 14, 19, 32, 36, 38, 39, 41, 44, 45, 48, 53, 54, and 56-57 have been fully considered and are persuasive. The rejections of Claims 14, 19, 32, 36, 38, 39, 41, 44, 45, 48, 53, 54, and 56-57 have been withdrawn. Claims 15 and 16 have been canceled, rendering those rejections moot.
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 1-3, 5, 14-16, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, and 62-63 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant Reply, filed 10/20/2025, page 9, para. 1, with respect to claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, and 63 have been fully considered and are persuasive. The rejections of Claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, and 63 have been withdrawn. Claims 15 and 16 have been canceled, rendering those rejections moot. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the amended claim set.
New Rejections
Claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, and 97-99 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.
Regarding claim 1, amended claim 1 now recites: “An engineered polypeptide comprising a degradation domain, wherein the degradation domain comprises a zinc finger domain comprising the amino acid sequence FCNQCGAS (SEQ ID NO: 3), and wherein the zinc finger domain is at least 85% identical to an amino acid sequence selected from SEQ ID NOs: 15, 21, 27, 32, 38, 60, 61, and 62.”
Paragraph [0041] provides support for the degradation domain comprising SEQ ID NO: 3. Paragraphs [0044]-[0047] provide support for the case wherein the zinc finger domain is at least 85% identical to an amino acid sequence selected from SEQ ID NOs: 15, 21, 27, 32, 38, 60, 61, and 62. However, no direct textual support is present for a combination of these two limitations.
Examining the claimed sequences, SEQ ID NOs: 7, 69, 70, and 71 possess the required FCNQCGAS motif; but as shown in the alignment below, these sequences only support an identity of approximately 92.5%. Therefore, no sequence-based support exists for this claim either. Consequently, this combination of limitations is new matter and therefore rejected.
Regarding claims 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, 98, and 99, these claims are all ultimately dependent upon claim 1 and therefore they all contain the same new matter and are rejected.
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Claims 1, 14, 19, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, and 98 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.
Regarding claim 1, claim 1 recites: “…wherein the zinc finger domain is at least 85% identical to an amino acid sequence selected from SEQ ID NOs: 15, 21, 27, 32, 38, 60, 61, and 62.” SEQ ID NO: 15 has 28 residues, and 85% identity to this amino acid means that 0.15*28= 4 residues may be substituted. This yields a genus size of at least 20^4 = 160,000 members.
In this case, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), 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).
The sequence space covered by this claim is substantial. Specifically, claim 1 encompasses 20^4 = 160,000 sequences at a minimum.
Applicant discloses an example of this degradation domain, but these examples are limited to primarily exploring the case of IKZF1-based constructs in the context of CD28 transmembrane domains, 4-1BB costimulatory domains, and CD3z signaling domains. Specifically, the example is SEQ ID NO: 19. However, SEQ ID NO: 19 does not exemplify the claimed sequence identity as shown below:
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SEQ ID NO: 19 is 96% identical to SEQ ID NO: 7 and therefore not representative of identities as low as 85%.
MPEP § 2163 (II.A.3.a.ii.) states that “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.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
At the time the invention was made, the level of skill for preparing and screening polypeptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally.
The provided example only represents a limited structural diversity. Since few species of polypeptides is taught within the claimed genus above and these polypeptides are not fully representative of the claimed genus, the instant claims above fail the written description requirement. A representative number of species has not been taught to describe this genus. A single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of polypeptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every polypeptide molecule recited by claim 1. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 1 is rejected.
Regarding claim 14, claim 1 is rejected as described above. Claim 14 has at least as much sequence space as claim 1, and no additional examples. Claim 14 is rejected.
Regarding claim 19, claim 19 recites a degradation domain wherein the degradation domain comprises an amino acid sequence that is at least 85% identical to an amino acid sequence selected from SEQ ID NOs: 7, 69, 70, and 71. Because these sequences are longer than exemplary sequences of claim 1, the genus of 19 has at least as much sequence space as claim 1, and no additional examples. Claim 19 is rejected.
Regarding claims 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, and 57, claim 1 is rejected as described above. These claims encompass the same sequence space as claim 1 with no additional examples. Consequently, claims 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, and 57 are rejected.
Regarding claim 62, claim 1 is rejected as described above. Claim 62 recites a nucleic acid encoding the engineered polypeptide of claim 1. Such a nucleic acid would cover at least as much sequence space as the amino acids of claim 1. No additional examples are provided, and therefore claim 62 is rejected.
Regarding claim 63, claim 62 is rejected as described above. Claim 63 recites a vector that comprises the nucleic acid of claim 62. Claim 62 encompasses at least the sequence space of claim 1. No additional examples are provided, and therefore claim 63 is rejected.
Regarding claim 97, claim 1 is rejected as described above. Claim 97 recites the case wherein the zinc finger domain is at least 90% identical to the amino acid sequence of SEQ ID NO: 15, 21, 27, 32, 38, 60, 61, or 62. The disclosed examples are not representative of this genus and furthermore, the genus of at least 20^2 sequences, not taking into account the different positions the substitutions can be at. Therefore, claim 97 is rejected.
Regarding claim 98, claim 19 is rejected as described above. Claim 98 recites the case wherein the two zinc finger domains comprise an amino acid sequence that is at least 90% identical to an amino acid sequence selected from SEQ ID NOs: 7, 69, 70, and 71. SEQ ID NO: 7 is 56 residues and therefore 90% identity allows for 20^5 sequences. Similar to claim 1, this genus is very large compared to the examples provided in the specification. Consequently, claim 98 is rejected.
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.
Claims 15, 16, and 19 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant Reply, filed 10/20/2025, page 12, para. 4, with respect to claims 15, 16, and 19 have been fully considered and are persuasive. The rejection of claim 19 has been withdrawn. Claims 15 and 16 have been canceled, rendering those rejections moot.
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.
Claims 1-3 and 5 were previously rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Response to Arguments
Applicant’s arguments, see Applicant Reply, filed 10/20/2025, page 13, para. 2 with respect to claims 1-3 and 5 have been fully considered and are persuasive. The rejection of claim 1 has been withdrawn. Claims 2, 3, and 5 have been canceled, rendering the rejections moot.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 12 and 14 were previously rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Byrne et al. (Byrne et al. Gene. 14;346:187-94. (2005)).
Response to Arguments
Applicant’s arguments, see Applicant Reply, filed 10/20/2025, page 13, para. 4 with respect to claims 1 and 14 have been fully considered and are persuasive. The rejection of claims 1 and 14 has been withdrawn. Claims 2 and 12 have been canceled, rendering the rejections moot.
Closest Prior Art
Brayshaw et al. (WO 20190002578, published 01/03/2019) discloses an Ikaros 1 protein SEQ ID NO: 27 from claim 6, aligned below with Applicant SEQ ID NO: 15.
SQ Sequence 28 AA;
Query Match 100.0%; Score 156; Length 28;
Best Local Similarity 100.0%;
Matches 28; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GERPFQCNQCGASFTQKGNLLRHIKLHS 28
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Db 1 GERPFQCNQCGASFTQKGNLLRHIKLHS 28
However, the sequences disclosed by Brayshaw at a minimum lack the Q6F mutation introduced by the present disclosure at position 6 as exemplified by Applicant SEQ ID NO: 7: GERPFFCNQCGASFTQKGNLLRHIKLHSGEKPFKCHLCNYACRRRDALTGHLRTHS. This Q to F substitution is novel because it is not found in the prior art. Also, the prior art does not provide a teaching, suggestion, or motivation to make this particular non-conservative substitution in this particular position. Therefore, this substitution is non-obvious.
Conclusion
No claim is allowed.
Claims 1, 14, 19, 22, 24, 27, 29, 32, 36, 38, 39, 41, 44, 45, 48, 50, 53, 54, 56, 57, 62, 63, and 97-99 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654