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 .
Election/Restrictions
Applicants’ election with traverse of Group I, Species A (i.e., R84Q and V85I, Seq ID No. 894) and Species B (i.e., a polynucleotide encoding the elected Species A) in the reply filed on 20 August 2026) is acknowledged. The traversal is on the ground(s) that search of Group I can be applied to subsequent groups (see Response received 20 August 2026, referred to herein as Remarks pg. 5, middle para). Regarding the species election Applicant argues there is no prior art disclosing a specific mutation at residue R84 according to Seq ID No: 2 and “no basis to view any one mutant species as an obvious variant of another” (see Remarks pg. 5 last para). Regarding the restriction of Groups, even if the prior art search for Group I could be applied to subsequent groups (which the examiner does not concede) the restriction would still be proper as the inventions have acquired a separate status in the art due to their recognized divergent subject matter (e.g., a polypeptide vs treatment with said polypeptide), require a different field of search (e.g., searching polypeptide sequences versus polynucleotide sequences, and are likely to raise different non-prior art issues under 35 USC 101 and/or 35 USC 112(a) (see Restriction mailed 22 June 2026 pg. 4, 1st para). Regarding the election of species Applicant appears to confirm that the variants are not obvious variants and whether or not the prior art discloses a variant is not relevant to structure function analysis of the variants.
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected groups, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 20 August 2026.
Status of the Claims
Claims 1-9 are currently pending and under consideration.
Priority
The instant application claims priority to foreign applications PCT/CN2023/072703 (referred to herein as ‘703 application) filed 17 January 2023 and CN202311057422.8 (referred to herein as ‘422 application) filed 22 August 2023.
It is noted the ‘703 application does not recite or contemplate a substitution at position V85 of Seq ID No: 2 (see instant claims 4-7).
It is noted the ‘422 application is not in English, therefore the examiner cannot determine if it discloses the claimed invention. For the purposes of applying prior art, the effective filing date for claims 4-7 is for the instant application filed 17 January 2024.
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 8-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) a mutant CD123 protein comprising a mutation at residue R84 according to Seq ID No: 2 that is not lysine (see claim 1), wherein the mutation is Q, N, or H (see claim 2), and specifically Q (see claim 3). This judicial exception is not integrated into a practical application because the product is not used in a method nor are additional elements recited. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (see below).
The following 35 USC 101 analysis using the Alice/Mayo test was performed (see MPEP § 2106(III)):
The broadest reasonable interpretation of the claims encompasses any CD123 protein with a substitution at the recited position which may also include substitutions at other positions.
Step 1: Yes, claim 8 is drawn to a product.
Step 2A Prong 1: Yes, claims 1-3 are drawn to a natural product as evidenced by (NCBI: XP_054533206. Interleukin-3 receptor subunit alpha isoform X2 Pan troglodytes. accessed online 8 September 2026; see also sequence comparison below; see also WO2023012367 A1 (referred to herein as Lepore), pg. 69 table 1).
Step 2A Prong 2: No, the claims do not recite additional elements that integrate the judicial exception (i.e., natural product) into a practical application.
Step 2B: No, there are no additional elements to consider recited in the claims. Regarding claims 8 and 9 which are drawn to a polynucleotide encoding the same and a cell comprising the mutant CD123 or polynucleotide encoding the same, given the mutant CD123 is naturally occurring it naturally follows there is a corresponding polynucleotide and cell expressing the mutant CD123.
Claim Rejections - 35 USC § 112(b)
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 1-9 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 1 is drawn to a mutant CD123 protein comprising a “mutation at residue R84 according to Seq ID No: 2”. The scope of the mutant CD123 protein is unclear. For example, is a deletion at position R84 within the scope of a “mutation at residue R84” given “mutation” would encompass a deletion, or alternatively, is the “mutation” limited to substitutions as the last line recites “mutation is to an amino acid”.
Claim 5 recites the limitation "the mutation at residue V85" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 5 depends from claim 3 which is drawn to position R84.
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.
Claims 1, 8, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US PG Publication 2016031996 A1 (referred to herein as Lopez, as cited on the IDS received 01/17/2024).
Lopez discloses an IL-3Rα antibody or antigen bind fragment thereof which specifically binds to an IL-3Rα epitope comprising one or more amino acid substitutions in Seq ID No: 1, in particular R84 substituted with alanine or lysine (see Lopez pg. 2 para [0025], pg. 5 para [0093, 0096, 0112, 0115, 0116], see claim 1). It is noted Lopez Seq ID No: 1 comprises the instantly claimed R84 position according to instant Seq ID No: 2 (see sequence comparison below). Furthermore, Lopez discloses, “in one example, the level of binding is detected by Western blotting or by fluorescence activated cell sorting (FACS) analysis of cells expressing the protein comprising the substitutions(s).” (see Lopez pg. 2 para [0038], emphasis added, see claim 9). Therefore, it naturally follows the cells expressing the protein comprise a polynucleotide encoding the mutant CD123 protein (see claim 8).
Claims 1-3, 8, and 9 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2023012367 A1 (referred to herein as Lepore) published 9 February 2023 and filed 5 August 2022.
Lepore discloses cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein (see Lepore abstract). Specifically, CD123 variants comprising R84Q (see Lepore figure 3-6 and 8, pg. 6, 4th para-pg. 7, 4th para, para spanning pgs. 35-36, pg. 36 last full sentence, pg. 72 lines 12-17). In addition, Lepore discloses mammalian cells expressing the CD123 isoform comprising at least one polymorphic allele in the nucleic acid encoding the isoform (see Lepore pg. 30, 6th para, pg. 72 lines 12-17). This is pertinent to instant claims 1-3, 8 and 9.
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 (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 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, 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 for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over WO2023012367 A1 (referred to herein as Lepore) published 9 February 2023 and filed 5 August 2022.
Lepore discloses cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein (see Lepore abstract). Plainly, Lepore’s invention is drawn to variant CD123 proteins that are functional identical to the naturally occurring CD123 while having differential binding to a given CD123 depleting agent (e.g., antibody) (Lepore pg. 3 lines 15-20. Pg. 10 lines 24-29, pg. 11 lines 12-16). Ultimately, the invention allows doctors to target CD123 which is also expressed on healthy cells with a depleting agent and supplement with engineer cells comprising a variant CD123 which does not bind the CD123 depleting agent; thereby, maintaining a population of cells with normal CD123 functions. One such variant comprises R84Q (see Lepore figure 3-6 and 8, pg. 6, 4th para-pg. 7, 4th para, para spanning pgs. 35-36, pg. 36 last full sentence, pg. 72 lines 12-17). Lepore teaches the CD123 variants also includes double mutants (see Lepore pg. 13 lines 4-12, pg. 33 lines 19-23) and teaches the epitope of the CD123 depleting agent includes residue V85 (i.e., T48, D49, E51, A 56, D57, Y58, S59, M60, P61 A62, V63, N64, T82, R84, V85, A86, N87, P89, F90, and S91) (see Lepore pg. 23 lines 1-5). Therefore, the ordinary artisan would have found it obvious to try combining substitutions at position V85 with the already made R84Q given the invention encompasses double mutants and V85 is relevant to antigen binding. This results in choosing from a list of 19 possible positions (i.e., a finite number of identified predictable potential solutions) which could have been pursued with a reasonable expectation of success (i.e., within the epitope). It is also noted that Lepore suggests the R84Q variant had a lower thermostability (see Lepore pg. 84 last para). Therefore, the ordinary artisan would be motivated to combine substitutions in order to increase the thermal stability of this particular mutant.
Claims 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over WO2023012367 A1 (referred to herein as Lepore) published 9 February 2023 and filed 5 August 2022 and Betts (see Betts and Russell (2003) Bioinformatics for Geneticists: Chapter 14 Amino Acid Properties and Consequences of Substitutions. John Wiley& Sons, Ltd. ISBNs: 0470843934, 0470843942).
The teachings of Lepore are set forth above. Briefly, Lepore renders obvious combing a second substitution at position V85 in a CD123 variant comprising a R84Q substitution. It is noted Lepore also teaches methionine, leucine, isoleucine, valine, and cysteine are members of the same large aliphatic, nonpolar group (see Lepore pg. 24 lines 5-6). In addition, Lepore discloses a CD123 sequence comprising Seq ID NO: 1 which is identical to instantly claimed Seq ID NO: 2 (see Lepore pg. 36, last para; see below).
Betts discloses valine, alanine, isoleucine (elected, i.e., Seq ID No: 894), leucine, and proline are amino acids with aliphatic side chains and methionine should also be considered within the same category despite having a sulfur atom (see Betts pg. 298 section 14.4.1.1, 1st para, pg. 300 section 14.5.2.2, pg. 301 section 14.5.4.2). The aliphatic side chains are known to be “very non-reactive, and are thus rarely involved directly in protein function, although they can play a role in substrate recognition” (see Betts pg. 298 section 14.4.1.1, 2nd para, pg. 300 section 14.5.2.3, pg. 301 section 14.5.4.2).
Therefore, the ordinary artisan would have found it obvious to substitute the naturally occurring valine at position 85 as taught by Lepore with either alanine, isoleucine, leucine, or methionine given this is a conservative substitution which will likely not affect CD123 function (as desired by Lepore) while effecting ligand recognition (i.e., the antibody as desired by Lepore). The ordinary artisan is therefore selecting from a finite number of positions and substitution with a finite number of possible amino acids. There is a reasonable expectation of success given V85 was a known residue within the epitope, and the amino acids are conservative substitutions. This is pertinent to instant claims 4-7. It is noted claim 5 is drawn to 7 possible substitutions wherein Betts and Lepore disclose more than half the possibilities (i.e., 4 and 5, respectively). It is also noted that the substitutions R84Q and V85I are set forth in instant Seq ID No: 894; therefore, Lepore and Betts render obvious Seq ID No: 894.
Sequence Comparison
Instant Seq ID No: 2 with R84Q compared to NCBI: XP_054533206 (underlined residue is position 84)
PNG
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600
825
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Greyscale
(Qy) Instant Seq ID No: 2 vs (Db) Lopez Seq ID No: 1
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811
710
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Greyscale
(Qy) Instant Seq ID No: 2 vs (Db) Lepore Seq ID No: 1
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763
721
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Greyscale
Conclusion
No claim allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Marone et al. (2023) Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy. J. Exp. Med. 2023 Vol. 220 No. 12, pgs. 1-24 e20231235.
The above cited reference teaches an R84Q substitution in CD123 in order to maintain a population of cells with normal CD123 functions. Marone also discloses the V85 position as within the relevant epitope and suggests variants could be generated in order to customize the response to a particular CD123 therapeutic agent.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H.A.P./Examiner, Art Unit 1644 /AMY E JUEDES/Primary Examiner, Art Unit 1644
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