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
Status of the Claims
1. Claims 1-27 are the original claims filed on 6/21/2023. In the Preliminary Amendment of 6/21/2023, Claims 1-17, 22-23 and 25-27 are amended and claims 18-21 and 24 are canceled. In the Reply of 4/2/2026, claims 1, 6-8, 10 and 12 are amended and claims 5, 9 and 15 are canceled.
Claims 1-4, 6-8, 10-14, 16-17, 22-23 and 25-27 are pending.
Election/Restrictions
2. Applicant's election with traverse of Group I in the reply filed on 4/2/2026 is acknowledged. The traversal is on the ground(s) that Payne (US 20220242931) fails to teach the amended claim 1 feature "wherein the autoantigen comprises or consists of a beta-1 subunit of the nicotinic acetylcholine receptor (nAChR), or an autoantigenic fragment thereof."
This is not found persuasive because open language “comprising” is not exclusive to “a beta-1 subunit”. The instant specification teaches a combination comprising both alpha and beta subunits for example at
[0053] “a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11).”
[0116] In embodiments, a genetically modified immune cell comprising an inventive CAAR with a beta-1 subunit autoantigen is in combination with a genetically modified immune cell comprising an inventive CAAR with an alpha-1 subunit autoantigen.
[0117] In embodiments, a genetically modified immune cell comprising an inventive CAAR with a beta-1 subunit autoantigen, e.g. comprising or consisting of a nicotinic acetylcholine receptor (nAChR) beta-1 subunit isoform 1 (SEQ ID NO: 3), beta-1 subunit isoform 2 (SEQ ID NO: 4), or the ECD of beta-1 subunit isoform 1 (SEQ ID NO: 21), or an autoantigenic fragment and/or combination and/or variant thereof, is in combination with a genetically modified immune cell comprising an inventive CAAR with an alpha-1 subunit autoantigen, e.g. alpha-1 subunit isoform 1 (SEQ ID NO: 1), alpha-1 subunit isoform 2 (SEQ ID NO: 2), extracellular autoantigenic part of an alpha-1 subunit isoform 1 (SEQ ID NO: 10), or a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11).
Generic claims 1, 26, and 53 of Payne recite not only open language for a CAAR but a generic extracellular domain comprising an acetylcholine receptor (AChR) autoantigen or fragment thereof.
The requirement is still deemed proper and is therefore made FINAL.
3. Claim 27 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/2/2026.
4. Claims 1-4, 6-8, 10-14, 16-17, 22-23 and 25-26 are the claims under examination.
Priority
5. USAN 18/268,803, filed 06/21/2023, is a National Stage entry of PCT/EP2021/ 087201, International Filing Date: 12/22/2021, claims foreign priority to EP 20216515.5, filed 12/22/2020. Priority filing for the CAAR is granted as of 12/22/2020.
Information Disclosure Statement
6. As of 6/1/2026, a total of one (1) IDS is filed: 6/21/2023. The corresponding initialed and dated 1449 form is considered and of record.
7. 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.
Objections
Specification
8. The abstract of the disclosure is objected to because it contains legal phraseology, i.e., said CAAR.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
9. The disclosure is objected to because of the following informalities:
a) The spacing of the lines of the specification is such as to make reading difficult. New application papers with lines 1 1/2 or double spaced (see 37 CFR 1.52(b)(2)) on good quality paper are required.
b) The use of the term ATCC, NSG, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
c) Amend the specification to replace “HEK293-Zellen” with “HEK293 cells.”
d) The specification on p. 8, line 15 uses the term “DaplO” that has no known meaning for a protein. If the intended meaning is dapl1 (Death associated protein like 1) then correction is required. If the intended meaning is Daplo (Dapagliflozin) then it is an oral prescription medication used primarily to manage Type 2 diabetes whose chemical structure shares no resemblance to a protein signaling domain:
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Appropriate correction is required.
Claim Objections
10. Claims 1, 4, 12(iv) and 16 are objected to because of the following informalities:
a) Amend claim 1 to recite “comprising the
b) Amend claim 4 to recite “or a fragment thereof.”
c) Amend claim 12(iv) to correct informalities without changing the scope of the claim:
iv. an intracellular signaling domain comprising a 4-1BB (CD137) co-stimulatory domain and a CD3 zeta chain (CD3ζ) signaling domainrespectively, or sequences with at least 80% sequence identity thereto.
d) Amend claim 16 to recite “A vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR) polypeptide according to claim 1.”
Appropriate correction is required.
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.
11. Claims 1-4, 6-8, 10-14, 16-17, 22-23 and 25-26 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) Claims 1-4, 6-8, 10-14, 16-17, 22-23 and 25-26 are indefinite for reciting “comprising” (open) and “consisting of” (closed) language for defining the same elements and features of the invention. MPEP 2111.03(I) and (II). The most common way to use both terms in the same claim is to use "comprising" at the start of the claim (the preamble) and "consisting of" (or a Markush group, e.g., “a member selected from the group consisting of…”) to limit a specific sub-element.
b) Claims 11-14 recite the limitation "the nucleic acid molecule". There is insufficient antecedent basis for this limitation in each of the claims. All of the rejected claims depend from claim 1 that does not recite a nucleic acid molecule.
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.
12. Claims 4, 6-8, 10, 12, and 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.
a) Claim 4 recites “wherein the autoantigen of the CAAR comprises an extracellular part of the nicotinic acetylcholine receptor (nAChR) or fragment thereof bound by autoantibodies” of claim 1. In view of the closed language of claim 1 consisting of a beta-1 subunit for the autoantigen, then the autoantigen of claim 4 cannot further comprise the subject matter of the “wherein” clause.
b) Claim 6 recites “consists of a nicotinic acetylcholine receptor (nAChR) beta-1 subunit isoform 1 (SEQ ID NO: 3), beta- 1 subunit isoform 2 (SEQ ID NO: 4), or an autoantigenic fragment and/or combination and/or autoantigenic variant with at least 80% sequence identity thereto.” In view of the closed language of claim 1 consisting of a beta-1 subunit for the autoantigen, then the autoantigen of claim 6 cannot further comprise beta- 1 subunit isoform 2 (SEQ ID NO: 4), or an autoantigenic fragment and/or combination and/or autoantigenic variant with at least 80% sequence identity thereto.
c) Claims 6-8 each recite “wherein the autoantigen of the CAAR comprises…an autoantigenic fragment and/or combination and/or autoantigenic variant with at least 80% sequence identity thereto.” An autoantigenic fragment and/or combination and/or autoantigenic variant is broader in scope than “an autoantigenic fragment thereof” of claim 1. An autoantigenic variant with at least 80% sequence identity thereto makes no reference to the autoantigen or antigenic fragment thereof of claim 1 irrespective of whether the language of claim 1 is closed or open.
d) Claim 10 recites “comprises or consists of a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11) a nicotinic acetylcholine receptor (nAChR),.. or autoantigenic variant with at least 80% sequence identity thereto.” In view of the closed language of claim 1 consisting of a beta-1 subunit for the autoantigen, then the autoantigen of claim 10 cannot further comprise or consist of a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11) a nicotinic acetylcholine receptor (nAChR),.. or autoantigenic variant with at least 80% sequence identity thereto.
e) Claim 12 recites “comprising or consisting of a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11), or of a nicotinic acetylcholine receptor (nAChR) beta-1 subunit isoform 1 (SEQ ID NO: 3), beta-1 subunit isoform 2 (SEQ ID NO: 4), an autoantigenic fragment and/or combination and/or autoantigenic variant with at least 80% sequence identity thereto.” In view of the closed language of claim 1 consisting of a beta-1 subunit for the autoantigen, then the autoantigen of claim 12 cannot further comprise or consist of a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11), or of a nicotinic acetylcholine receptor (nAChR) beta-1 subunit isoform 1 (SEQ ID NO: 3), beta-1 subunit isoform 2 (SEQ ID NO: 4), an autoantigenic fragment and/or combination and/or autoantigenic variant with at least 80% sequence identity thereto.
f) Claim 23 is broadening for the second cell comprising an autoantigenic fragment and/or combinations thereof. The autoantigenic fragment is not defined as being a fragment for any one of the preceding autoantigens for the second cell, and therefore is broadening.
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.
Rejections Maintained
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.
13. The rejection of Claim(s) 1-4, 5-8, 10-11, 16-17, under 35 U.S.C. 103 as being unpatentable over Payne et al (US 20220242931; filed 5/12/2020) is maintained.
Applicants allege Payne fails to teach the amended claim 1 feature "wherein the autoantigen comprises or consists of a beta-1 subunit of the nicotinic acetylcholine receptor (nAChR), or an autoantigenic fragment thereof."
Response to Arguments
AS regards claim 1, this is not found persuasive because open language “comprising” is not exclusive to “a beta-1 subunit”. The instant specification teaches a combination comprising both alpha and beta subunits for example at
[0053] “a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11).”
[0116] In embodiments, a genetically modified immune cell comprising an inventive CAAR with a beta-1 subunit autoantigen is in combination with a genetically modified immune cell comprising an inventive CAAR with an alpha-1 subunit autoantigen.
[0117] In embodiments, a genetically modified immune cell comprising an inventive CAAR with a beta-1 subunit autoantigen, e.g. comprising or consisting of a nicotinic acetylcholine receptor (nAChR) beta-1 subunit isoform 1 (SEQ ID NO: 3), beta-1 subunit isoform 2 (SEQ ID NO: 4), or the ECD of beta-1 subunit isoform 1 (SEQ ID NO: 21), or an autoantigenic fragment and/or combination and/or variant thereof, is in combination with a genetically modified immune cell comprising an inventive CAAR with an alpha-1 subunit autoantigen, e.g. alpha-1 subunit isoform 1 (SEQ ID NO: 1), alpha-1 subunit isoform 2 (SEQ ID NO: 2), extracellular autoantigenic part of an alpha-1 subunit isoform 1 (SEQ ID NO: 10), or a combination of extracellular autoantigenic parts of alpha-1 isoform 1 and beta-1 isoform 1 subunits (SEQ ID NO: 11).
Generic claims 1, 26, and 53 of Payne recite not only open language for a CAAR but a generic extracellular domain comprising an acetylcholine receptor (AChR) autoantigen or fragment thereof: “an extracellular domain comprising an acetylcholine receptor (AChR) autoantigen or fragment thereof.”
As regards claim 2, Payne teaches auto-antibody mediated neuromuscular disorders where the autoantibody binds to the CAAR at [0017, 0110].
AS regards claim 3, Payne teaches specific neuromuscular disorders at [0110].
AS regards claim 4, Payne teaches the autoantigen comprising an extracellular part of nAChR at [0112].
AS regards claims 6-8, Payne teaches an autoantigenic fragment at [0005, 00009, 0011].
AS regards claim 10, Payne autoantigenic variants for the autoantigen at [0183] that comprise truncations or mutations of AChR based on major disease epitopes.
AS regards claim 11, Payne teaches: transmembrane domains at [0127]; intracellular domain/co-stimulatory domain at [0007]; signaling domain at [0007]; and a signal (leader)/linker/spacer at [0125-0126, 0150, 0244].
AS regards claims 16-17, Payne teaches polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR in the abstract and at [0010].
As regards Claims 22-23 and 26, Payne teaches recombinant cells at [0014, 0043].
Currently, autoimmune-associated neuromuscular disorders such as mild MG is treated with acetylcholinesterase inhibitors to inhibit acetylcholine breakdown. Moderate to severe MG is treated with prednisone, anti-proliferatives such as mycophenolate or azathioprine, complement inhibitors, and rituximab in more advanced disease, strategies that can be associated with infection due to immune suppression and other side effects. Payne provides the motivation to make and use a CAAR that achieves a more specific and effective treatment of for example, myasthenia gravis.
The rejection is maintained.
Conclusion
14. No claims are allowed.
15. The sequence of SEQ ID NO: 11 is free from the art.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
Prosecution Insights