DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group II (drawn to an isolated polynucleotide) in the Response filed on February 5, 2026 is acknowledged. Upon further consideration, the previous Species Election Requirement set forth in the Office Action mailed on November 5, 2025 is withdrawn.
Claims 1-22 and 25-29 have been canceled.
Claims 30-50 have been added.
Claims 23, 24, and 30-50 are pending and currently under consideration.
3. 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.
4. Claims 49 and 50 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.
Claims 49 and 50 encompass a method of producing a humanized anti-C1q antibody by culturing the host cell of claim 24. There is insufficient antecedent basis for this limitation of a humanized anti-C1q antibody in the previous claim 24 which is further depended upon claim 23. Claims 23 and 24 do not recite humanized anti-C1q antibody.
5. 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.
6. Claims 23, 24, and 30-50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
an isolated polynucleotide comprising a nucleic acid sequence encoding a humanized anti-C1q antibody or an antigen binding fragment thereof comprising:
a) a VH of any one of the SEQ ID NOs 1-4 or the amino acid sequence having at least 95% sequence identity to any one of SEQ ID NO:1-4 and HVR-H1 of SEQ ID NO:23, HVR-H2 of SEQ ID NO:24, and HVR-H3 of SEQ ID NO:25, and
b) a VL of any one of SEQ ID NOs: 5-8, or an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 5-8 and HVR-L1 of SEQ ID NO: 30, HVR-L2 of SEQ ID NO:31, and HVR-L3 of SEQ ID NO:32, and
a host cell comprising he polynucleotide, and a method of producing the anti-C1q antibody by culturing the host cell for expressing the VH and VL and recovering the anti-C1q antibody VH and VL.
does not reasonably provide enablement for more. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The claims are drawn to an isolated polynucleotide comprising a nucleic acid sequence encoding an IgG antibody heavy chain or antigen-binding fragment thereof comprising HVR-H1 of SEQ ID NO:23, HVR-H2 of SEQ ID NO:24, and HVR-H3 of SEQ ID NO:25, or HVR-L1 of SEQ ID NO:30, HVR-L2 of SEQ ID NO:31, and HVR-L2. Independent claim 23 does not recite any antigen specificity for the IgG antibody.
Dependent claims 49 and 50 are drawn to a method of producing a humanized anti-C1q antibody, a heavy or light chain thereof.
The specification discloses the generation of fully humanized anti-C1q antibodies from murine hybridoma M1 (e.g. see [0247]). These humanized antibodies all have specific sequences for the VH and VL.
However, there does not appear to be sufficient guidance in the specification as filed as to how the skilled artisan would make and use the various amino acids sequences recited in the instant claims. A person skill in the art would not be able to predict which additional CDRs are to be paired together to form a functional antibody with no antigen specificity.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function.
For example, Chiu et al. (Antibodies 2019, 8,55; 1-80) teach that of all of the six CDRs, the VH CDR3 most often has changes in conformation with unbound and bound structures are compared. In addition, differences in the orientation of VL with respect to VH are often seen and the induced-fit mode of binding introduces plasticity into the antigen-binding site, expanding antibody diversity beyond that resulting from amino acid residue changes (e.g. see page 5). Further, Chiu et al. teach that studies conducted with multiple institutes in predicting CDRs structure do not appear to yield reliable results (e.g. see 1.2.6. Antibody Modeling in page 6).
Sela-Culang et al. (Frontiers in Immunology, 2013, Vol. 4, Article 302, pages 1-13) shows that each CDR has its own unique amino acid composition different from the composition of other CDRs (e.g. see right col. in page 5). In addition, Sela-Culang et al. teach that each CDR has a unique set of contact preferences, therefore, favoring certain amino acids over others (see lines spanning pages 5-6). Sela-Culang et al. also teach that many attempts to isolate and design individual antigen-binding CDR or CDR derived peptides have failed and it is possible that a CDR on its own may not fold to the same conformation as in the context of the entire Fab crucial for antigen binding (e.g. see first full paragraph in the left col. in page 7).
Therefore, it is unlikely that the antibodies encoded by the polynucleotide as defined by the instant claims, which contain not all CDRs (e.g. only three CDRs from either heavy chain or light chain) would have the binding function as recited in the instant methods in claims 49 and 50.
Further, it has been well established in the art that the antigen binding specify is critical to how the skilled artisan would make the antibodies. However, the instant claims do not recite an antigen specificity for C1q.
The specification provides insufficient direction or guidance regarding how to make or use the IgG antibodies as broadly defined by the claims other than the anti-C1q antibodies with defined six CDRs for heavy chain and light chain or defined VH and VL. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the written disclosure alone.
In view of the quantity of experimentation necessary, the limited working example, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trials and errors to make and use the IgG antibody with less than six CDRs without antigen specificity.
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
8. Claims 23, 24, and 30-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US 10,723,788 (‘788 Patent) in view of Presta (US 6,727,056).
Instant claims are drawn to an isolated polynucleotide comprising a nucleic acid sequence encoding an IG antibody having the amino acid sequences of the recited VH and three VH CDRs or VL and the three VL CDRs, a host cell, and a method of producing the IgG have VH and/or VL sequences.
The claims in the ‘788 Patent are drawn to an antibody Fab fragment that binds to C1q comprising a heavy chain of SEQ ID NO:1 and light chain of SEQ ID NO:2. SEQ ID NO:1 and SEQ ID NO:2 are 100% identical to the instant SEQ ID NO:3 and SEQ ID NO:7, respectively. See sequence alignments below.
Instant SEQ ID NO:3 (Qy) alignment:
RESULT 2
US-15-360-549-1
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 1, US/15360549
Patent No. 10723788
GENERAL INFORMATION
APPLICANT: YEDNOCK, TED
APPLICANT: SANKARANARAYANAN, SETHU
APPLICANT: LEVITEN, MICHAEL
APPLICANT: ROSENTHAL, ARNON
TITLE OF INVENTION: ANTI-COMPLEMENT FACTOR C1Q FAB FRAGMENTS AND USES THEREOF
FILE REFERENCE: ANH-011.01
CURRENT APPLICATION NUMBER: US/15/360,549
CURRENT FILING DATE: 2016-11-23
PRIOR APPLICATION NUMBER: 62/259,227
PRIOR FILING DATE: 2015-11-24
NUMBER OF SEQ ID NOS: 12
SEQ ID NO 1
LENGTH: 229
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 642; Length 229;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAELKKPGASVKVSCKSSGYHFTSYWMHWVKQAPGQGLEWIGVIHPNSGSINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAELKKPGASVKVSCKSSGYHFTSYWMHWVKQAPGQGLEWIGVIHPNSGSINY 60
Qy 61 NEKFESRVTITVDKSTSTAYMELSSLRSEDTAVYYCAGERDSTEVLPMDYWGQGTTVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFESRVTITVDKSTSTAYMELSSLRSEDTAVYYCAGERDSTEVLPMDYWGQGTTVTVS 120
Qy 121 S 121
|
Db 121 S 121
Instant SEQ ID NO:7 (Qy) alignment:
RESULT 2
US-15-360-549-1
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 1, US/15360549
Patent No. 10723788
GENERAL INFORMATION
APPLICANT: YEDNOCK, TED
APPLICANT: SANKARANARAYANAN, SETHU
APPLICANT: LEVITEN, MICHAEL
APPLICANT: ROSENTHAL, ARNON
TITLE OF INVENTION: ANTI-COMPLEMENT FACTOR C1Q FAB FRAGMENTS AND USES THEREOF
FILE REFERENCE: ANH-011.01
CURRENT APPLICATION NUMBER: US/15/360,549
CURRENT FILING DATE: 2016-11-23
PRIOR APPLICATION NUMBER: 62/259,227
PRIOR FILING DATE: 2015-11-24
NUMBER OF SEQ ID NOS: 12
SEQ ID NO 1
LENGTH: 229
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 642; Length 229;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAELKKPGASVKVSCKSSGYHFTSYWMHWVKQAPGQGLEWIGVIHPNSGSINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAELKKPGASVKVSCKSSGYHFTSYWMHWVKQAPGQGLEWIGVIHPNSGSINY 60
Qy 61 NEKFESRVTITVDKSTSTAYMELSSLRSEDTAVYYCAGERDSTEVLPMDYWGQGTTVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFESRVTITVDKSTSTAYMELSSLRSEDTAVYYCAGERDSTEVLPMDYWGQGTTVTVS 120
Qy 121 S 121
|
Db 121 S 121
The claims in the ‘788 Patent differ from the instant claims by not claiming a nucleic acid, and a host cell, and a method of producing the antibody.
Although the claims at issue are not identical, they are not patentably distinct from each other because it was well known that the proteins in the US patents listed above can be made using established cloning techniques. For example, Presta teaches human IgG Fc variant consisting amino acid substitutions (e.g. see Table 6 in col. 57-58).
Presta further teaches that plasmid containing the nucleic acids encoding the human IgG Fc variants are co-transfected into an adenovirus transformed human embryonic kidney cell line, and method of producing the Fc variants by culturing the cells and harvest the secreted Fc variant followed by purifying the Fc variant via Protein G SEPHAROSE (e.g. see Example 4 in col. 54).
It would thus be obvious to produce the anti-C1q antibody recited in the claims in the conflicting ‘788 Patent following the procedures taught in Presta, namely cloning the cDNAs encoding the IgG antibody and inserting the cDNA into a vector, transfecting the vector into a host cell, then producing the Fc variant by culturing the host cell under conditions wherein the antibodies are produced and purifying the Fc variants. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since the anti-C1q antibody having identical amino acid sequences to the IgG antibodies encoded by the instantly recited polynucleotide can be produced by well-known recombinant methods using nucleic acid, vector, host cell taught by Presta. As such, the species of anti-C1q antibody in the claims in the conflicting ‘788 Patent would render the genus of IgG antibody encoded by the nucleic acid, host cell, and method of producing the antibody recited the instant claims obvious.
9. No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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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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/CHUN W DAHLE/Primary Examiner, Art Unit 1641