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 .
Applicant's preliminary amendment, dated March 28, 2024, has been received. By means of this submission, Applicant has amended claims 3-5, 8, 10-11, 15-16, 19, 20, 23, 26, 28-29, 31, 33, and 36, and cancelled claims 6-7, 9, 12-14, 17-18, 21-22, 24-25, 27, 32, and 34-35.
Claims 1-5, 8, 10-11, 15-16, 19-20, 23, 26, 28-31, 33, and 36 are pending in the application and under examination before the Office.
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on application CN202111149114.9 filed in China on September 29, 2021. However, it is noted that no certified English translation of said application has been filed. A certified English translation of this application is required to properly assert priority. See 37 CFR 1.78.
Absent this required English translation of the foreign priority document, the claims are given a priority date of their earliest English filing date, which is March 28, 2024.
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.
Claims 1-5, 8, 10-11, 15-16, 19-20, 23, 26, 28-31, 33, and 36 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 1, 5, 8, 11, 16, 19, 20, 23, 26, 28, and 36 contain exemplary claim language that raises ambiguity as to whether or not the recited examples are intended to limited the claims, through the claims’ use of the terms "such as", "e.g.", and "preferably".
Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. MPEP 2173.05(d).
For the purposes of claim construction, any exemplary claim language is being interpreted as optional.
Claims 19 and 28 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 19 and 28 recite the limitation of "the number of the first protein functional region is 1, and the number of the second protein functional region is 2". It is not readily apparent what this limitation means, or how it is intended to meaningfully limit the claim. It is not clear if the number is meant to merely be a descriptive label, or if there is one first protein functional region and two second protein functional regions. Clarification is required.
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 1-5, 8, 10-11, 15, 20, 26, 28-31, 33, and 36 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
"[T]he purpose of the written description requirement is to 'ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.'" Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), "[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
"[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A "representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) ("The '128 and '485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus."). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number" of species.
The "structural features common to the members of the genus" needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 ("[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims."). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 ("The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.")
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is "had possession of the claimed subject matter as of the filing date. Demonstrating possession "requires a precise definition" of the invention. To provide this precise definition" for a claim to a genus, a patentee must disclose "a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus" (see Amgen at page 1358).
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – "a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials", which may be present in "functional terminology when the art has established a correlation between structure and function" (Amgen page 1361).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guide lines for claims drawn to antibodies, which can be found at www.uspto.gov/sltes/default/files/docurrienfcs/amgenJ22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen.
In the instant case, the specification discloses a bispecific antibody that binds LAG3 and PD-1. However, the claims broadly encompass any bispecific antibody that binds LAG3 with the claimed complementarity determining regions (CDRs) and a second domain that targets any other target. In contrast to Applicant's disclosure of the specific anti-LAG3/anti-PD-1 antibody, the instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus or structure common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus of the claimed bispecific antibody.
A "representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The "structural features common to the members of the genus" needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Here, the claims are directed to a genus of antigen-binding immunoglobulin molecules are defined by their desired binding to an antigen and function of such binding.
It is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Protein Eng Des Sel. 2009 Mar;22(3):159-68; see page 159, right column, first paragraph: "Selection of such libraries to a given antigen can give rise to several hundreds to thousands of different antibodies.") The high degree of polymorphism in antibody generation evidences a lack of structure-function correlation for antibodies. This is especially true as the second target of the bispecific antibody is completely undefined in claim 1.
Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of bispecific antibody that binds LAG3 and any other target broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
Applicant is invited to amend the claims to recite the CDR sequences of the anti-PD-1 binding domain in order to obviate this rejection.
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.
Claim Rejections - 35 USC § 102
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 1-5, 8, 10-11, 15-16, 19-20, 23, 26, 28-31, 33, and 36 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Zhang (WO2022188867A1, machine translation attached).
Zhang teaches a bispecific antibody, comprising a first antigen binding domain that binds to PD-1, and a second antigen binding domain that binds to LAG3, wherein the LAG3 domain is an IgG antibody and the PD-1 domain is an scFv, the two domains are connected by a linking fragment (i.e., a linker), and the heavy chain constant region is IgG1 with L234A and L235A mutations, according to the EU numbering system (page 26, first paragraph, also see page 17, fourth paragraph).
Zhang further teaches sequences identical to those as instantly claimed to describe the light and heavy chains of the LAG3 and PD-1 binding domains (pages 9, 12, and 14).
Zhang further teaches a pharmaceutical product comprising the above bispecific antibody and one or more pharmaceutically acceptable excipients (page 3).
Zhang further teaches isolated nucleic acid molecules, vectors, and host cells of the above, and that this bispecific antibody is useful for treating cancer (page 16).
While Zhang does not teach that the anti-LAG3 antibody binds to human LAG3-mFc with an EC50 value of less than 0.2 nM, the anti-LAG3 antibody of Zhang is identical to the anti-LAG3 antibody of the claims, and therefore would possess identical functional properties as the claimed antibody. If the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d.
Applicant is invited to submit an English translation of the certified copy of the foreign priority document in order to address this issue.
Double Patenting
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.
Claims 1-5, 8, 10-11, 15-16, 19-20, 23, 26, 28-31, 33, and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 11-13, 15, and 18 of copending Application No. 18/696,559 in view of Li (US20190321466A1) and Deak (US20180326054A1).
The '559 application claims an anti-LAG3 antibody or an antigen-binding fragment thereof, comprising identical sequences as to those claimed in the instant application (claim 1).
The '559 application further claims the antibody or the antigen-binding fragment thereof is selected from a Fab, a Fab', an F(ab')2, an Fd, a dAb, a complementarity determining region fragment, a single chain fragment variable, a humanized antibody, or a chimeric antibody (claim 3), which is prejudicial to instant claim 3.
The '559 application further claims that the antibody binds to human LAG3-mFc with an EC50 value of less than 0.2 nM (claim 4), which is prejudicial to instant claim 4.
The '559 application further claims that the antibody comprises a non-CDR region derived from a species other than murine (claim 5), which is prejudicial to instant claim 5.
The '559 application further claims an isolated nucleic acid molecule, encoding the above anti-LAG3 antibody (claim 11), which is prejudicial to instant claim 29.
The '559 application further claims a recombinant vector, comprising the above isolated nucleic acid molecule (claim 12), which is prejudicial to instant claim 30.
The '559 application further claims a host cell, comprising the above isolated nucleic acid molecule (claim 13), which is prejudicial to instant claim 31.
The '559 application further claims a pharmaceutical composition, comprising the above antibody or the antigen-binding fragment thereof (claim 15), which is prejudicial to instant claim 33.
The '559 application further claims a method for treating and/or preventing a tumor or anemia (claim 18), which is prejudicial to instant claim 36.
However, the '559 application does not claim a bispecific antibody.
Li teaches an anti-PD-1 antibody with identical sequences as those recited in instant claims 16, 19, and 23 (para. 0012-0016). It is also noted that Applicant's specification at page states that the claimed sequences are taught by Chinese Patent Publication No. CN 106967172A (or No. CN 106977602A), which is the foreign priority document of the Li publication.
Li further teaches that the above anti-PD-1 antibody may be an scFv or part of a bispecific antibody (para. 0028).
Li further teaches that the above anti-PD-1 antibody is useful for treating tumor or anemia (para. 0076).
Deak teaches a bispecific antibody, comprising a first antigen binding domain that binds to PD-1, and a second antigen binding domain that binds to LAG3 (para. 0007).
Deak further teaches that above bispecific antibody comprises an Fc domain of human IgG1 subclass with the amino acid mutations L234A and L235A, according to the EU numbering system (para. 0088), which is prejudicial to claims 8 and 26.
Deak further teaches that the two domains of the bispecific antibody may be connected with a linker (para. 0106), and the linker may be GGGGS (para. 0207).
Deak further teaches that this bispecific antibody is useful for treating cancer (para. 0006 and 0132).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '559 application with the teachings of Li and Deak to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since the '559 application, Li, and Deak are all concerned with cancer immunotherapy. Bispecific antibodies that bind LAG3 and PD-1 and their use in cancer treatment were known in the art, according to Deak. The '559 application claims one such anti-LAG3 antibody, and Li teaches one such anti-PD-1 antibody. One of ordinary skill could apply the sequences of the '559 application and Li to the bispecific antibody of Deak by simple substitution, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1642
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