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 .
Claims 1-4 and 6-21 are pending and examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/20/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 20 is objected to because of the following informalities: the claim recites “any of claims 14”, however, only one claim is recited. It is suggested that claim 20 be amended to recite, “of claim 14”. Appropriate correction is required.
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 1, 3, 6-9, 11, 13, 14, 16 and 18-21 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 a monoclonal antibody that comprises the variable heavy chain of SEQ ID NO: 4 and the CDRs of SEQ ID NO:s 1-4 and the variable light chain of SEQ ID NO: 8 and the CDRs of SEQ ID NO: 5-7, and methods of inhibiting or treating an influenza A infection, does not reasonably provide enablement for an antibody without at least an identified 6 CDRs found in the variable light and heavy chains and the treatment or inhibition of an influenza A infection. 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 the invention commensurate in scope with these claims.
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 skill in the art to practice the claimed invention.
The claims are drawn to an antibody that comprises either SEQ ID NO:s 1-3 or an antibody comprising SEQ ID NO:s 1-3 or an antibody comprising the heavy chain of SEQ ID NO: 4 and methods of treating or inhibiting an influenza A infection, such as a H1N1 or swine influenza infection.
Applicants have tested the ability of antibody raH1N1 (which comprises the heavy and light chains of SEQ ID NO:s 4 and 8 and 9, and the CDRs of SEQ ID NO:s 1-3 and 5-7, which inhibit or treat an influenza A H1N1 infection, including a swine influenza infection. However, applicants have not testing whether an antibody only comprising the heavy chain CDRs or heavy chain can inhibit or treat an influenza infection.
Thus, the claim is directed to a broad class of antibodies, only defined by its function and amino acid sequences that might be required or might be fragments thereof or variants thereof and CDRs or heavy variable domain. However, relative to the claimed openness to fragments of the CDRs, the specification does not give one of ordinary skilled in the art enough information to choose candidate antigen binding structures from the vast number of options that fall within the fragments of the claimed CDRs, and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. This decision reaffirmed the prior decision made by the Federal District Court in Amgen Inc. v. Sanofi, Aventisub LLC., 987 F.3d 1080 (Fed. Cir. 2021).
The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality … running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, the Supreme Court found that Amgen failed to enable all that it claimed, even if allowing for a reasonable degree of experimentation. Id. at 613; see also Baxalta Inc. v Genentech, Inc., 81 F.4th 1362, 1367, 2023 USPQ2d 1103 (Fed. Cir. 2023) ("[t]he facts of this case are more analogous to—and are, in fact, indistinguishable from—those in Amgen. We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."). Moreover, "[w]e see no meaningful difference between Wands' ‘undue experimentation’ and Amgen's ‘[un]reasonable experimentation’ standards. Id. at footnote 4. See also Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024), which explains that regardless of the technology the Wands factors should be used when assessing enablement.
However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613.
In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
This case is akin to the issue in Amgen Inc. v. Sanofi, Aventisub LLC, in which the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Sanofi-Aventisub at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a ‘vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure.
The instant claims are directed to a class of antibodies that include “a ‘vast’ number of antibodies comprising an antibody having 3 defined CDRs or one defined heavy chain and still be able to bind an influenza A virus, including an H1N1 and swine influenza virus and treat or inhibit the virus, in view of teachings for the specification. It would be necessary to first generate and then screen each candidate antibody and fragments thereof, with the recited function to determine whether it met the functional limitations of treating or inhibit the claimed influenza infections. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
With regard to the antibody raH1N1, the instant specification does not disclose any common structural feature delineating which of the claimed variants of raH1N1 will have the function of bind to an influenza A virus, H1N1 or swing influenza virus and inhibit or treat an infection by influenza, or how to distinguish structures with this function from structures without.
The instant claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the antigen binding CDRs they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
The Supreme Court’s 2023 decision in Amgen v. Sanofi, which mainly involves the enablement requirement, states that “where a patentee purports to invent an entire genus, it must enable the entire genus”; “disclosing how to produce some antibodies that perform a specified function is not equivalent to disclosing how to produce all such antibodies – and it is the latter that petitioners claim as their invention”; S. Ct.
The specification does not reasonably provide enablement to make the invention of claims 1, 3, 6-9, 11, 13, 14, 16 and 18-21 as it is currently written. The specification does reasonably provide enablement to make and use the invention of antibody raH1N1 as discussed above.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary, the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
In addition, any CDR mutation, which can happen when you recombine all these CDRs into different species is not predictable. This is evidenced by the fact that 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 as evidenced by Rudikoff (Proc Natl Acad Sci USA 1982 Vol 79 page 1979). Rudikoff teaches that the alteration of a single amino acid in a single CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (entire article, Abstract).)
Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies not having all of the relevant functional complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Claims 13-17 and 19-21 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 inhibiting an influenza A infection by administering a monoclonal antibody comprising the CDRs of SEQ ID NO:s 1-3 and 5-7, does not reasonably provide enablement for preventing an influenza A infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims. The claims are drawn to a preventing an influenza virus infection by administering an antibody that comprises either SEQ ID NO:s 1-3 or an antibody comprising SEQ ID NO:s 1-3 and 5-7 or an antibody comprising the heavy chain of SEQ ID NO: 4 or an antibody comprising the heavy chain CDRs of SEQ ID NO:s 1-3 and the light chain of SEQ ID NO: 8.
State of the prior art/Predictability of the art. The state of the art related to treating or vaccinating against influenza viruses recognizes that seasonal influenza vaccines are most effective against influenza viruses that circulate throughout the year. One example of a seasonal influenza vaccine is Fluzone®. Vaccines such as this possess a split version of influenza viruses, which contains multiple proteins of each influenza virus, such as the HA and NA proteins. The literature provided by Sanofi-Pasteur (see attached package insert) indicates in section 12.1 that seasonal influenza vaccines are protective against influenza illness in 50% of those that are vaccinated. This document also discusses that antibodies against one influenza virus provide limited protection against other influenza viruses.
Working examples. No working example is disclosed in the specification in which the claimed composition is determined to prevent an influenza viral infection. Applicants do test the therapeutic effect of a monoclonal antibody raH1N1 that comprises SEQ ID NO:s 4 and 8 and the constatnt region of SEQ ID NO:9. Viral inhibition was achieved in pigs infected with virus. However, these tests did not establish that an influenza viral infection can be prevented as claimed.
Guidance in the specification. The specification provides guidance towards preventing or treating influenza infections by administering the claimed composition.
Amount of experimentation necessary. Additional research is required in order to determine how effective preventing an influenza virus infection by administering any the claimed antibody (antigen binding molecule) to a subject.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
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 2 and 7 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.
Claim 2 recites the limitation "the H1N1 antibody binding molecule" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an antigen binding molecule and, accordingly, the identification/description is indefinite.
Claim 7 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of different antigen binding molecules is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each antigen binding molecule possesses distinct structures and functions. For example, the claim recites, monoclonal antibody, tri-specific antibody and CAR T cells.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim(s) 1, 2, 4, 7-15 and 17-21 are rejected under 35 U.S.C. 102a1 as being anticipated by Crowe et al. (US PGPub 2013/0289246).
The claimed invention is drawn to an Influenza A antigen binding molecule comprising a heavy chain variable region; wherein the heavy chain variable region comprises three complementarity determining regions (CDRs) referred to as CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and wherein the H1N1 antigen binding molecule further comprises a light chain variable region and wherein the light chain variable region comprises three complementarity determining regions (CDRs) referred to as CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively.
The light chain comprises SEQ ID NO: 8.
The claimed invention is also drawn to a method of treating or inhibiting an influenza A viral infection in a subject comprising administering to the subject an Influenza A antigen binding molecule comprising a heavy chain variable region; wherein the heavy chain variable region comprises three complementarity determining regions (CDRs) referred to as CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and wherein the H1N1 antigen binding molecule further comprises a light chain variable region and wherein the light chain variable region comprises three complementarity determining regions (CDRs) referred to as CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively.
The light chain comprises SEQ ID NO: 8.
Crowe et al. teach a monoclonal antibody 5J8, which is specific for H1N1. [see Table B and Paragraphs 283-285] Crowe et al. also teach the administration of 5J8 to mice in order to inhibit or treat an influenza virus infection. SEQ ID NO 77 presents the heavy chain of 5J8, which comprises SEQ ID NO:s 1-3 of the instant invention and SEQ ID NO: 79 of 5J8 comprises SEQ ID NO:s 5-7 of the instant invention and SEQ ID NO: 79 is identical to SEQ ID NO: 9 of the instant invention. Crowe et al. also teach that the virus is a swine H1N1 influenza virus. [see paragraph 284 and Table 14] Therefore, Crowe et al. anticipate the instant invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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