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
Applicant’s claim to priority from Foreign application EP20186492.3 filed 07/17/2020 and PCT/EP2021/070181 filed 07/19/2021 is hereby acknowledged.
Election/Restrictions
Applicant’s election without traverse of Invention Group II in the reply filed on 11/19/2025 is acknowledged:
Invention Group II, claims 4-8, 10-11 and 19-24, drawn to a method for treating a primary or secondary immunodeficiency, or a pathology that displays an immunosuppressed phenotype.
Applicant's election with traverse of Species listed below in the reply filed on 11/19/2025 is acknowledged as follow:
Species Group A (claims 1, 4, 6, 8, 13 and 25): a L1 having a sequence having 100, 99, 98, 97, 96, 95, 90, 85 or 80% identity with:
SEQ ID NO: 1,
Species Group B (claims 4, 13 and 25): a suppressor or inhibitor selected from the group consisting of:
A polynucleotide that is an antisense construct, an antisense oligonucleotide, RNA interference construct or siRNA or a polynucleotide coding for it.
Species Group C (claims 23 and 27): an antisense oligonucleotide (ASO) comprising a nucleic acid sequence that targets:
SEQ ID NO: 5.
Species Group D (claims 23 and 27): a CRISPR/Cas9 component that is a sgRNA comprising a nucleic acid sequence that targets or is complementary to:
SEQ ID NO: 9,
The traversal is on the ground(s) that “the Office Action improperly mixes an election of species with a restriction between groups. The Action simultaneously demands election of a single species and imposes restrictions between Groups A and D, C and D, and A, B, and C.
By requiring both, the Action creates inherently inconsistent results: electing any one of Groups A-D necessarily leaves unelected species in the other groups, so the additional "restriction between groups" nullifies the species election in those unelected groups.”
This is not found persuasive because during the phone call on October 24, 2025, Examiner specifically responded to the request for clarification by explaining that Applicant, knowing best which species is encompassed within the invention group II elected, should pick all compatible (overlapping) elements listed in Group A-D for one invention.
It appears that Applicant wished to elect more than one invention, including in the response, an ASO and a CRISPR-Cas system sgRNA. However, there are rare instances, in the art, in which a CRISPR-Cas system is augmented by the use of an ASO. Therefore, Examiner will consider individually the ASO and sgRNA as independent inhibitors, as well as a combination of both, when and if claimed.
Although the claims are drafted in a way that combines multiple inventions, it is possible to examine portions of the claims that address a specific elected invention.
The requirement is still deemed proper and is therefore made FINAL.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Application Status
This Application is a National Stage entry Application under 35 U.S.C. §371 of PCT/EP2021/070181 filed 07/19/2021.
Claim amendments filed 11/19/2025 are hereby acknowledged. Claims 2-3, 9, 12 and 14-16 are cancelled. Claims 1, 4-8, 10-11, 13, 17-27 are pending. Claims 1, 13, 17-18, and 25-27 are withdrawn. Therefore, claims 4-8, 10-11, and 19-24 are under consideration in this office action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 01/17/2023, 08/08/2025 and 01/30/2026 are hereby acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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, or are listed on a submitted IDS, they have not been considered.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter.”
In the current case, the view numbers for the partial views for Figures 1 to 19 that appear on several sheets are followed by "(n/n)." (n being the number of pages in which the same figure number appears) instead of a capital letter such as FIG. 1A, FIG. 1B, etc.
The drawings are objected to for the following reasons:
37 C.F.R. 1.84 states “Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.”
In the current case, the words in Figure 2a are illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - Sequences appearing in the drawings ( Figures 13g, 13h and 16c) are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (page 16, line 23; page 32, line 2). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms “GlutaMAX”, “Viogreen”, “Vioblue”, “Pacific Blue”, “Vio770”, “FACSAria” (page 30), “Dynabeads” (pages 30, 31, 37-38), “Alexa Fluor” (pages 33, 34), “Triton-X100” (pages 34, 35, 37, 38, 43), “Eclipse” (page 35), “Nucleofector” (page 36), “Qubit”, “Bolt” (page 37), “Maxwell” (page 38), “Ribogone”, “SMARTer”, “NextSeq” (page 39), “GoTaq” (page 36, 42), “TapeStation” (pages 39, 43), “MinION” (page 43), “AMPure” (page 44), which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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.
Claim Objections
Claim 4 is objected to because of the following informalities:
The claim recites “ a) a polynucleotide, selected from the group consisting of :antisense construct, antisense oligonucleotide, RNA interference construct or siRNA or a polynucleotide coding for it,”. The claim should recite “ a) a polynucleotide selected from the group consisting of: antisense construct, antisense oligonucleotide, RNA interference construct, or siRNA or a polynucleotide coding for it”. The position of the commas makes it clearer that “a polynucleotide coding for it” refers to the siRNA.
The claim also recites in d) “the polynucleotide as defined in a) or at least one component of c”. The claim should recite “the polynucleotide as defined in a) or at least one component of c)”.
Claim 4 is also objected to because the term “and” is missing in the recited Markush group. The claim should recite:
“ c) a CRISPR/Cas9 component, and
d) a host cell genetically engineered expressing a polypeptide or antibody or comprising the polynucleotide as defined in a) or at least one component of c)”.
Claim 11 is objected to because of the following informalities:
The claim recites “The method according to claim 4, …, wherein said suppressor or inhibitor or the cell is injected in the tumor site, or delivered by nanoparticles specifically to the site of interest.” Commas are missing between “inhibitor” and “or the cell” and “is injected”.
Claim 19 is objected to because of the following informalities:
The claim recites “wherein the method is performed by immunotherapy”. The method is a “method for treating a primary or secondary immunodeficiency, or a pathology that displays an immunosuppressed phenotype, comprising at least one step of administering to an individual in need a suppressor or inhibitor of (long
interspersed element 1) LINE1 (L1) expression”, therefore the method is an immunotherapy. The claim should read “wherein the method is an immunotherapy”.
Claim 22 is objected to because of the following informalities:
The claim recites: “The method according to claim 7, wherein said inhibitory
nucleic acid is a 2'-deoxy-2'-fluoro- -D-arabinonucleid acid (FANA) ASO, and comprises one or more modified bands or bases, or said inhibitory nucleic acid comprises one or more modified bands or bases.
The claim should recite “The method according to claim 7, wherein said inhibitory
nucleic acid is a 2'-deoxy-2'-fluoro-β-D-arabinonucleic acid (FANA) ASO, and comprises one or more modified bands or bases, or said inhibitory nucleic acid comprises one or more modified bands or bases.
Claim 24 is objected to because of the following informalities:
The claim recites: “The method according to claim 10, wherein said
immunotherapy comprises administration of an immune checkpoint inhibitor, chimeric antigen receptor (CAR)-expressing immune effector cells, or bath, wherein said immune checkpoint inhibitor is an or comprises one or more anti-CD137 antibodies; anti-PD-I (programmed cell death 1) antibodies; anti-PDLI (programmed cell death ligand 1) antibodies; anti-PDL2 antibodies; or anti-CTLA-4 antibodies.”
The claim should recite “The method according to claim 10, wherein said
immunotherapy further comprises administration of an immune checkpoint inhibitor, chimeric antigen receptor (CAR)-expressing immune effector cells, or both, wherein said immune checkpoint inhibitor is an, or comprises one or more anti-CD137 antibodies; anti-PD-1 (programmed cell death 1) antibodies; anti-PDL1 (programmed cell death ligand 1) antibodies; anti-PDL2 antibodies; or anti-CTLA-4 antibodies.”
Appropriate correction is required.
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.
Claim 4 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.
Regarding claim 4, the sequences described in SEQ ID NOs: 1-3 are not L1 sequences as traditionally defined. It is not clear whether these sequences are new variants of the traditionally known human L1, of consensus sequence as described by Scott (Scott, A.F. et al. “Origin of the Human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence”. Genomics, Vol . 1 (1987), pp: 113-125) and revised in Crowther (Crowther, P.J. et al. “Revised genomic consensus for the hypermethylated CpG island region of the human L1 transposon and integration sites of full length L1 elements from recombinant clones made using methylation-tolerant host strains”. Nucleic Acids Research, Vol. 19, No. 9 (1991), pp: 2395-2401) and NCBI-pdf1 (“Human LINE-1 transposon (L1Hs) DNA”, GenBank Accession No: X58075.1, published May 15, 1991 ). It is not clear whether L1 refers to the reverse transcriptase, ORF1 or ORF2 sequences.
A search with alignment of sequences shows that only a portion of L1 sequence is comprised within SEQ ID NOs: 1-3; since these sequences seem to be the result of integration and fusion in genes such as IFNGR2, RAB22A and ARCP2 with L1 sequences, it is misleading to name these sequences L1.
Thus, it is also not clear whether the inhibitors of L1 can also be considered inhibitors of the species cited in claim 4, or whether the inhibitors should be specifically inhibitors to the recombinant products of SEQ ID NOs: 1-3. The language used in the claim is confusing.
Claim 10 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 claim recites : “The method according to claim 4, wherein the cell or the
inhibitor or suppressor of LINE1 is administered in combination with an immunotherapy or with a radiotherapy or chemotherapeutic agent or with targeted therapies which promote raising of new antigens and immunity response or with immunity system adjuvants.”
It is unclear what type of therapy or agent is included in those “which promote raising of new antigens and immunity response”. It is also unclear what are the “new antigens”.
Claim 22 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 claim recites “The method according to claim 7, wherein said inhibitory
nucleic acid is a 2'-deoxy-2'-fluoro- -D-arabinonucleid acid (F ANA) ASO, and comprises one or more modified bands or bases, or said inhibitory nucleic acid comprises one or more modified bands or bases.”
The Specification does not define what the term “bands” means in this context. Therefore, the modification pattern is not well understood.
Claim Rejections - 35 USC § 112(d)
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.
Claim 19 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.
The claim recites “wherein the method is performed by immunotherapy”. The method is a “method for treating a primary or secondary immunodeficiency, or a pathology that displays an immunosuppressed phenotype, comprising at least one step of administering to an individual in need a suppressor or inhibitor of (long
interspersed element 1) LINE1 (L1) expression”, therefore the method is an immunotherapy. The claim seems to be drawn to the definition of the therapy, but does not add any new step to the method. Therefore, the claim does not further limits the claim it depends on.
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.
Claims 4, 5, 7, 10-11 and 20-22 are rejected under 35 U.S.C. §102(a)(1) as being anticipated by Bondarev ( Bondarev, I. et al. WO 2007/106561 A2; published September 20, 2007; listed on IDS filed 01/30/2026), as evidenced by Zhang (Zhang, X. et al. “New understanding of the relevant role of LINE1 retrotransposition in human disease and immune modulation”. Frontiers in Cell and Developmental Biology, Vol. 8 (2020), p: 657).
Regarding claim 4, it recites: “A method for treating a primary or
Secondary immunodeficiency, or a pathology that displays an immunosuppressed phenotype, comprising at least one step of administering to an individual in need a suppressor or inhibitor of (long interspersed element 1) LINE1 (L1) expression or a cell as defined in claim 1, wherein L1 comprises a sequence having 100, 99, 98, 97, 96, 95, 90, 85, or 80% identity with SEQ ID NO: 1 or 2 or 3, wherein the suppressor or inhibitor is at least one molecule selected from the group consisting of:
a polynucleotide, selected from the group consisting of :antisense
construct, antisense oligonucleotide, RNA interference construct or siRNA or a polynucleotide coding for it,
b) a vector comprising or expressing the polynucleotide as defined in a),
c) a CRISPR/Cas9 component,
d) a host cell genetically engineered expressing a polypeptide or antibody
or comprising the polynucleotide as defined in a) or at least one component of c.”
The claim is interpreted as requiring an inhibitor of LINE-1, which inherently can repress any LINE-1 of any sequence.
Bondarev teaches that LINE-1 is responsible for telomere lengthening in telomerase negative cancer cells and support their immortalization (see page 8, lines 19-29). Therefore, Bondarev teaches method for treating cancer involving targeted therapies focusing on L1 reverse transcriptase (L1RT) and the use of L1RT inhibitors (see abstract, and page 8, lines 30-31; page 9, lines 17-29; and see claims 36 and 43).
Regarding claims 5 and 7, Bondarev teaches that the inhibitor can be a nucleic acid construct, an antibody or fragment thereof, or a dsRNA corresponding to a defined target region in the selected RT (see page 11, lines 4-20 and see below):
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Bondarev also teaches that an oligonucleotide sequence complementary to a template sequence contained with the RNA component of the RT, antisense constructs against telomerase RNA, sequence-specific peptide-nucleic acids directed against telomerase RNA can be inhibitors (see page 17, lines 19-26).
Therefore, Bondarev teaches a larger genus comprising species of inhibitors to LINE-1 encompassing species recited in claims 4 , 5 and 7.
As evidenced by Zhang, hypomethylated and highly expressed LINE-1 has been found in autoimmune diseases (see page 4, “LINE-1 and autoimmune disease” section). Zhang teaches that LINE-1 is not only responsible for cancer development, but also for immunosuppression (see pages 4-5, sections “LINE-1 and tumor immunity”).
Therefore, Bondarev teaches a method for treating a primary or secondary immunodeficiency or a pathology that displays an immunosuppressed phenotype, comprising administering to an individual a L1 inhibitor, that can be an antisense nucleic acid.
Regarding claim 10, Bondarev teaches combination of the L1RT inhibitor with an anticancer agent, chemo or radiation (see page 37, lines 3-15; see claims 1-16). Bondarev teaches anticancer agents such as 5-FU, floxuridine, bleomycin, mitomycin, methotrexate among others (same paragraph).
Regarding claim 11, Bondarev teaches that for easily accessible tumors such as breast or prostate tumors, the inhibitor and/or combination of anticancer drugs can be administered by targeted and direct needle injection to the site of the lesion (see page 31, lines 6-10).
Regarding claim 20, Bondarev teaches the treatment of cancer and metastasis (see page 4, lines 2-5; see claim 2).
Regarding claim 21, Bondarev teaches that the cancer can be lung cancer or colorectal cancer (see page 5, lines 7-13).
Regarding claim 22, Bondarev teaches that the inhibitory nucleic acid comprises modified bases, e.g., “ a lipid-conjugated thio-phosphoramidate N3’-P5’ oligonucleotide, a peptide-nucleic acid (page 17, lines 19-26). Bondarev also teaches that the RNA can be a 2’-O-methyl modified RNA and/or a phosphorothioate oligonucleotide (see page 31, lines 15-26).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 19 and 24 are rejected under 35 U.S.C. §103 as being unpatentable over Bondarev ( Bondarev, I. et al. WO 2007/106561 A2; published September 20, 2007; listed on IDS filed 01/30/2026), as evidenced by Zhang (Zhang, X. et al. “New understanding of the relevant role of LINE1 retrotransposition in human disease and immune modulation”. Frontiers in Cell and Developmental Biology, Vol. 8 (2020), p: 657), as applied to claims 4 and 10 above, and in view of Mishra (Mishra, J. et al. "Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis." Critical Reviews in Oncology/Hematology, Vol. 86 (2013), pp: 232-250).
It is noted that claims 4 and 10 are anticipated by Bondarev as evidenced by Zhang. The rejection of claims 4 and 10 is described above.
Regarding claims 19 and 24, Bondarev, as evidenced by Zhang, renders elements of claims 4 and 10 obvious. However, Bondarev does not teach elements of claims 19 and 24, i.e. Bondarev does not teach an immunotherapy (claim 19), nor any specific antibody such as an anti-CD137 antibody, an anti-PD-1 antibody, and anti-PDL1 antibody, and anti-PDL2 antibody nor an anti-CTLA-4 antibody (claim 24).
However, Mishra teaches that colon cancer can be treatment-resistant, and would benefit from combinatorial approach to enhance cancer cell apoptosis (see title).
Mishra teaches targeted immunotherapy using monoclonal antibodies targeting immune effector cells, such as anti-CD137 mAb, anti-CD47 mAb (see page 240, left column, “Monoclonal Antibodies (mAb)” paragraph).
Mishra teaches the limitations of immunotherapies alone (see page 236, right column, “Limitations of immunotherapies” paragraph), and of cancer vaccines alone (see page 237, right column, “Limitations of cancer vaccines” paragraph).
Mishra also teaches that interfering nucleic acids is a new therapeutic approach, notably siRNA for knocking out undesirable gene products, for instance hTERT, which is highly active in 90% of all tumors expressing telomerase reverse transcriptase (see page 242, section 4.2, left column, lines 1-14).
Mishra specifically teaches “combinatorial approach” (page 244, section 5). Mishra teaches that direct effects of chemotherapy on tumor or host environment, such as induction of tumor cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for enhancement of immunotherapy by chemotherapy (see page 245, section 5.2).
Therefore, it would have been obvious to one of ordinary skills before the effective filing date, to have combined the antisense nucleic acid targeting LINE-1 as described by Bondarev, with an antibody that directly effects the tumor microenvironment, such as an antibody against CD-137, as taught by Mishra. One with ordinary skills in the art, motivated in abrogating treatment resistance in colon cancer, could have performed this modification with a reasonable expectation of success and arrived at the claimed invention.
Allowable Subject Matter
A specific inhibitory nucleic acid comprising a sequence of nucleotides that are complementary to 10 to 50 consecutive nucleotides of SEQ ID NO: 1 or 2 or 3, appears to be free of prior art.
An ASO comprising a sequence capable of hybridizing or complementary to a sequence comprising SEQ ID NO: 1 or 2 or 3 appears to be free of prior art.
An inhibitory nucleic acid that comprises SEQ ID NO: 5 appears to be free of prior art.
A sgRNA comprising a nucleic acid sequence that targets or is complementary to SEQ ID NO: 9 appears to be free of prior art.
Claims 6, 8 and 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 4-5, 7, 10-11, 19-22 and 24 are rejected.
Claims 4, 6, 8, 11, 19 and 22-24 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA G DACE DENITO whose telephone number is (703)756-4752. The examiner can normally be reached Monday-Friday, 8:30-5:00EST.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636