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 .
Response to Amendment
In response to sequence compliance pre-exam notice, applicant filed on 01-24-2024, a substitute specification including the original claims, which was cancelled with a preliminary amendment filed 06/05/2023. The claims section is stamped “CLEAN VERSION”, which indicates it was submitted as a part of the substitute specification, not reinstatement of previously cancelled claims. If applicant wishes a previously canceled claim to be reinstated, it may be reinstated only by adding the claim as a “new” claim with a new claim number.
Claims 1-44 were cancelled. Claims 45-62 are pending and examined on merits.
Claim Rejections - 35 USC § 112
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 45 and 46 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir.1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of the skilled in the art to practice the claimed invention.
The scope of the claim
Claims 45 and 46 are drawn to a genus of anti-gp120 neutralizing antibodies in a combination therapy with cabotegravir. An antibody no longer can be claimed by reciting a target where it binds to according to the Supreme Court Amgen Inc v. Sanofi (5/18/23). The scope potentially encompasses “quintillion” unique species as discussed in Amgen v. Sanofi, 598 U.S. 594 (2023). Briney et al. (Nature 2019. 566:393-399) was cited in the Supreme Court decision to determine a potential scope of the asserted antibody claims. The instant antibody claims are similar to those asserted Amgen claims in that both claims recite epitope structures, instead of claimed antibody structures.
The amount of direction provided by the inventor and existence of working examples
The specification discloses art-known anti-gp120 antibodies.
The level of predictability in the art
US 10562960 B2 (the ‘960 patent) teaches antibody structures bind to gp120 on HIV-1 and neutralizes HIV-1. The neutralizing antibodies taught by the ‘960 patent have particular amino acid structures. One cannot predict other antibody structures based on the target structure.
20200223907 A1 (“the ‘907 publication”) also teaches antibody structures bind to gp120 on HIV-1 and neutralizes HIV-1.
However, those antibodies binding to gp120 on HIV-1 and neutralizing HIV-1 do not possess the common binding structures, although have the same function. Unlike other proteins evolutionarily conserved such as DNA polymerases, antibody proteins do not have common core structures for their target binding activities.
The Supreme Court (Amgen, 2023) held that the Amgen application was not enabled for the genus of antibodies that (1) bind to specific amino acid residues on PCSK9, and (2) block PCSK9 from binding to LDL receptors, even though Amgen disclosed numerous PCSK9 antibodies that met (1) and (2) requirements. Amgen’s arguments that scientists could make other antibodies that meet these two functions. The case law applies to the instant claims which require a genus of multi-specific anti-IL-13 and IL-22 and/or anti-serum albumin.
The quantity of experimentation needed to make or use the invention based on the disclosure
Based on the content of the disclosure and the state of art, in view of the recent Supreme Court ruling regarding nature of an antibody invention, a skilled artisan, through extensive trial-and-error experimentation, would have to make antibodies, validate their functions. For all of these reasons, the specification does not enable one of ordinary skill in the art to make and/or use what is claimed except for the antibodies claimed by structures in the claims not rejected here.
Priority
The effective filing date is 12/07/2020, the filing date of 63/122,031.
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.
Claim(s) 45 and 46 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20200223907 A1 (“the ‘907 publication”, Date Published, 2020-07-16).
Claims 45 and 46 are drawn to a combination HIV-1 therapy with cabotegravir and anti-gp120 antibodies.
The ‘907 publication teaches neutralizing HIV-1 antibodies binding to gp120 (see claims) and also teaches a combination therapy with cabotegravir and antibody. Note the entire specification, especially Para [0215] for a combination therapy.
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.
Claim(s) 47-62 is/are rejected under 35 U.S.C. 103 as being unpatentable over the ‘907 publication (cited above) as applied to claims 1 and 2 above in view of US 10562960 B2 (the ‘960 patent) and further in view of US 20160347816 A1 (the ‘816 publication, Published 2016-12-01).
Claims 47-51, and 55 are drawn to a specific antibody (or its fragment) sequences in combination HIV-1 treatment with cabotegravir.
The ‘907 publication teaches a combination HIV-1 treatment, administering an anti-gp120 antibody and cabotegravir. The ‘907 publication also teaches “three clonal family variants of an antibody with neutralizing activity were found, among which the antibody named N6 (isolated as an IgG1 mAb) was the most potent and broad (FIG. 1B)” and “(448) To define the structural mechanisms by which N6 might mediate such potency and breadth, structural analysis of the antigen-binding fragment of N6 (Fab) in complex with HIV gp120 proteins from strains with different sensitivity to VRC01-class antibodies was performed (see FIGS. 9-13).”
The ‘907 publication does not teach the specific sequences recited in the instant claims.
However, the ‘960 patent teaches the gp120 antibody sequences as claimed in instant claims 47-51 (antibody structures by sequences), 55 (antibody fragment), and 56 (Fv, Fab, F(ab')2, scFV or a scFV2) Note the sequence alignments below.
Neither the ‘960 patent nor the ‘907 publication teaches a recombinant constant domain comprising one or more amino acid modifications that increase the half-life of the antibody or those specific modification recited in claims 52-54 .
However, the ‘816 publication teaches:
[0250] In several embodiments, the constant region of the antibody includes one or more amino acid substitutions to optimize in vivo half-life of the antibody. The serum half-life of IgG Abs is regulated by the neonatal Fc receptor (FcRn). Thus, in several embodiments, the antibody includes an amino acid substitution that increases binding to the FcRn. Several such substitutions are known to the person of ordinary skill in the art, such as substitutions at IgG constant regions T250Q and M428L (see, e.g., Hinton et al., J Immunol., 176:346-356, 2006); M428L and N434S (the “LS” mutation, see, e.g., Zalevsky, et al., Nature Biotechnology, 28:157-159, 2010); N434A (see, e.g., Petkova et al., Int. Immunol., 18:1759-1769, 2006); T307A, E380A, and N434A (see, e.g., Petkova et al., Int. Immunol., 18:1759-1769, 2006); and M252Y, S254T, and T256E (see, e.g., Dall'Acqua et al., J. Biol. Chem., 281:23514-23524, 2006).The disclosed antibodies and
[0369] Clause 17. The antibody of clause 16, wherein the antibody is an IgG1 and the modification that increases binding to the neonatal Fc receptor comprises M428L and N434S amino acid substitutions.
For claim 59 drawn to administering separately, claim 60 to drawn to administering simultaneously, and claim 62 drawn to administering once every month, once every 2 months, once every 3 months, or once every 6 months, US 20160347816 A1, Published 2016-12-01 teaches “[0603] In some methods, two or more monoclonal antibodies with different binding specificities are administered simultaneously, in which case the dosage of each antibody administered falls within the ranges indicated. Antibody is usually administered on multiple occasions. Intervals between single dosages can be, for example, weekly, monthly, every three months or yearly. “
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention with a reasonable expectation of success since the claimed combination therapy is taught and the claimed antigen binding portion of the claimed antibody structure is also taught. The Fc modification is also taught in the prior art. One of ordinary skill in the art would have been motivated to arrive at the claimed invention since the antibody modification improves in vivo half-life of the antibody.
SEQ ID NO: 1 search result
Sequence 1, US/15559791
Patent No. 10562960
LENGTH: 122
Query Match 100.0%; Score 663; Length 122;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNF 60
Qy 61 GGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVV 120
Qy 121 SA 122
||
Db 121 SA 122
SEQ ID NO: 2 search result
Sequence 2, US/15559791
Patent No. 10562960
LENGTH: 103
Query Match 100.0%; Score 548; Length 103;
Best Local Similarity 100.0%;
Matches 103; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPS 60
Qy 61 RFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK 103
|||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK 103
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/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641