DETAILED ACTION
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 election with traverse of a method of treatment comprising administering an SAA inhibitor, wherein the inhibitor is an antibody inhibitor of SAA1, and wherein the condition is sepsis, in the reply filed on 12/2/25 is acknowledged. Upon reconsideration, the restriction between SAA1 and SAA2 species is withdrawn.
Applicant's traversal is on the grounds that since both SAA proteins and SAA inhibitors are integral to the same inventive idea, restricting the claims to only one species would narrow the scope and fail to capture the inventive contribution as a whole. This is not persuasive since the claims recite two distinct and non-overlapping species of invention. The species lack unity of invention since the SAA inhibitor does not have a special technical feature that defines the contribution over the prior art of WO 2010/036962 for the reasons of record (see also prior art cited below). Applicant further argues that according to MPEP 803, restriction is only proper if there would be a serious burden. This is not found persuasive because undue burden is irrelevant to the restriction practice for cases filed under 35 U.S.C 371 (see MPEP Chapter 1800).
The requirement is still deemed proper and is therefore made FINAL.
Claims 2-5 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Claims 6-12 are being acted upon.
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 6 and 8 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 6 is indefinite in the recitation that the inhibitor is selected form the group consisting of small molecule inhibitors, bispecific antibodies, bispecific peptides, “and” inhibitory antibodies “or” antibody mimetics directed against SAA. As an initial matter, the use of both “and” and “or” is indefinite, since it is unclear if the group consisting of is intending to include all of the recite elements or not. It is also not clear if the recitation of “directed against SAA” relates only to the antibody mimetic embodiment, or whether the claims intend all of the recited inhibitors to be “directed against SAA”.
Regarding claim 8, the phrase "e.g.’" or “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(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.
Claims 6-12 are rejected on the basis that they contain 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 methods of treatment by administering rSAA or an inhibitor of SAA 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: An rSAA protein and an inhibitor of SAA are completely structurally unrelated, nor do they belong to the same chemical class. For example, rSAA protein and a small molecule inhibitor or an antibody inhibitor are not structurally similar. Nor do the claims encompass a common use. For example, rSAA increases SAA downstream effects and is used in treating conditions in which inflammation is suppressed, whereas the SAA inhibitors inhibit SAA function and is used in conditions with excessive inflammation.
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.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 6-12 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of SAA inhibitors.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The instant claims are directed to a methods of treating conditions or diseases characterized by dysregulated inflammation comprising administering an inhibitor of SAA. Theis encompass a extremely large genus of structurally distinct molecules. For example, the claims encompass antibody inhibitors, small molecule inhibitors, nucleic acids, or peptides. Furthermore, SAA consists of a family of proteins that has pleiotropic functions and despite more than fifty years since its discovery, its true biological functions remain enigmatic (See Ji, 2025). Thus, there is not an art recognized correlation between structure and function. Regarding antibody inhibitors, the claims encompass methods employing a broad genus of structurally different antibodies. For example, the claims encompass bispecific antibodies, monoclonal antibodies, antibody mimetics or antibodies derived from different species, such as human, mouse, or rat that would have different VH and VL sequences. Furthermore, the claims encompass a genus of antibodies that bind to different epitope regions of a genus of SAA proteins, or those with different affinities or pharmokinetic properties. The state of the art is such that antibody based therapy is extremely complex and requires a deep understanding of protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system. Furthermore, the development of candidate antibodies involves a complex process of clinical and preclinical evaluation that include identification of the physical and chemical properties of the antibody (see Scott et al, pages 278-279, of record). Antibodies have a wide range of pharmacokinetics, effector functions, size and immunogenicity, affinities and avidities, all of which effect the function of each antibody in vivo (see Scott et al., 2012, page 278, in particular). Additionally, antibody variable regions are composed of a heavy and light chain, each involved in providing for binding specificity. Variability in the antigen binding site is achieved by V(D)J recombination via heavy and light chain pairing, with the most diverse regions being the 6 CDR regions in the heavy and light chain. For example Janeway, teaches that the antibody repertoire in humans is at least 1011, with a large degree of diversity in both heavy and light chains. See, for example, Rabia, 2018, which teaches that the maximal chemical diversity of antibody CDRs is unimaginably large and is extremely challenging to define the sequence determinant of antibody specificity (see page 4). The specification does not provide a correlation between structure and function for the inhibitors as broadly claimed. The only species of inhibitors specifically disclosed by the instant specifical is HDL and mc1 and mc29 monoclonal antibodies. It is noted that Mc1 and Mc29 are disclosed in the prior art as being detrimental and reducing survival from sepsis (see US 2015/0023957). The specification does not provide any guidance regarding what types of inhibitors are to be used in each of the distinct disease encompassed by the present claims. No species of bispecific peptides, antibody mimetics or small molecule inhibitors are disclosed by the instant specification. The disclosed species are not sufficiently representative of the broad genus of inhibitors that function in the genus of disease encompassed by the present claims.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of inhibitors encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning – i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Claims 6-12 are rejected under 35 U.S.C. 112, 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. Specifically, the specification provides insufficient guidance to practice the method as broadly claimed.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, see In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) states, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” “The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling” (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. With these teachings in mind, an enabling disclosure, commensurate in scope with the breadth of the claimed invention, is required.
The instant claims are directed to a method of treating any condition or disease characterized by excessive inflammation by administering a genus of SAA inhibitors. The claims encompass a large genus of different diseases with different etiologies and pathological mechanism, including autoimmune disease, burns, infections, cancer, Alzheimer’s disease, and sepsis. The claims also encompass an extremely large genus of structurally distinct inhibitors. For example, the claims encompass antibody inhibitors, small molecule inhibitors, nucleic acids, or peptides.
Furthermore, the state of the art is such that SAA consists of a family of proteins that has pleiotropic functions and despite more than fifty years since its discovery, its true biological functions remain enigmatic (see Ji, 2025). SAA can have pro-inflammatory effects, but also can play a protective role during inflammation, and the nature of its impact is highly context dependent (see Ji). See also White, 2021, which teaches that SAA is a pleiotropic agent mediating effects through multiple receptors, and can have both pro and anti-inflammatory effects. For example, White teaches that SAA may actually contribute to dampening excessive inflammation during influenza virus infection or SAR-COV-2 infection, and using an inhibitor of SAA to treat inflammatory responses caused by influenza or corona virus infection, as specifically recited in the present claims, would be highly unpredictable. Furthermore, the claims encompass using a genus of structurally distinct inhibitors. For example, the state of the art is such that design of antibody therapy is extremely complex and requires a deep understanding of protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system. Furthermore, the development of candidate antibodies involves a complex process of clinical and preclinical evaluation that include identification of the physical and chemical properties of the antibody (see Scott et al, pages 278-279, of record). Thus, making and using the genus of different inhibitors, including antibodies that function to treat diseases ranging from cancer, infection, Alzheimer’s disease, or autoimmune disease, would be highly unpredictable.
Given the unpredictably of the art and the breadth of the claims, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the claims. However, the only examples regarding inhibitors in the specification is an in vitro example studying the effects of SAA on neutrophils, whereby it has both anti-inflammatory and pro-inflammatory activity that is concentration dependent. The specification discloses monoclonal antibodies mc1 and mc29 that can block the inhibitory action of SAA on neutrophils in vitro, and discloses an effect of temperature of SAA activity, but that the consequences of any temperature induce aggregation are “unknown”. Regarding the mc1 and mc29 antibody, these have been tested in a model of sepsis in the prior art, and shown to reduce survival (see US 2015/0023957). On the other hand, the ‘957 publication teaches a different type of antibody that binds a specific epitope in SAA with a unique mechanism of action in reducing HMGB1 release that can treat sepsis. In other words, the state of the art is such that each inhibitor of SAA can have functionally distinct mechanisms, and the effect of any inhibitor in treating the genus of different diseases with different pathological mechanisms would be highly unpredictable. Thus, while it may be possible to use a specific inhibitor, such as the HMGB1 reducing epitope specific antibody disclosed in the ‘957 publication, for treating specific diseases such as sepsis, the present claims broadly encompass treating a genus of pathologically distinct diseases with a genus of structurally and functionally distinct SAA inhibitors. This would be highly unpredictable based on the current state of the art. No guidance is provided regarding which of the numerous pleiotropic functions of the genus of SAA proteins should be targeted to treat the genus of diseases encompassed by the instant claims. No examples of treating any disease with any inhibitor are disclosed, nor are sufficient species of inhibitors disclosed. Thus, based on the unpredictability of the art, the lack of guidance provided by the instant specification and the breadth of the claims, it would require undue experimentation to practice the method as broadly claimed..
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.
Claim(s) 6-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010/036962 (of record).
WO 2010/036962 teaches a method of treating a human subject by administering to the subject an antisense RNA inhibitor of SAA, wherein the subject has chronic sepsis (see pages 81-82, in particular). WO 2010/036962 teaches inhibitors of SAA1 (See page 2, particular). WO 2010/036962 teaches said inhibitor as part of a pharmaceutical composition with a pharmaceutically acceptable carrier (see page 9, in particular). WO 2010/036962 teaches that after a first dose of the inhibitor, the subject’s condition is evaluated, e.g. by measuring temperature whereby the number and strength of doses are adjusted according to the subject’s needs. WO 2010/036962 teaches that after treatment the subjects temperature is lowered relative to the levels of prior to the treatment. In the method of WO 2010/036962, the act of administering the inhibitor lowers the temperature of the treated subject, which would be within the scope of the “actively” inducing a lower temperature. While WO 2010/036962 does not explicitly teach inducing normal temperature, it would be obvious to treat the patient until the sepsis and inflammation subsequently have resolved and body temperature has returned to normal for a human subject, i.e. 37 degrees C.
Claims 6-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0023957, in view of WO 2010/036962 (both of record) and US 20160333081.
The ‘957 publication teaches a method of treating sepsis in a subject comprising administering to the subject an antibody inhibitor of SAA (See pages 2, 11-12, in particular). The ‘957 publication teaches treating human subjects (see page 11, in particular). The ‘957 publication teaches giving repeated doses of the antibodies (see paragraph 60 and 121, in particular). The ‘957 publication teaches SAA neutralizing antibodies that bind to various epitopes within SAA1 or SAA2 (see Table 2, in particular). The ‘957 publication teaches said antibody inhibitor as part of a pharmaceutical composition with a pharmaceutically acceptable carrier (see page 11, in particular).
The reference differs from the claimed invention in that it does not explicitly teach actively inducing normal temperature in the subject.
The ‘081 publication teaches that fever is a well-known symptom of sepsis, and that treatment methods for sepsis can comprise administration of secondary agents that include NSAIDs, anti-infectives, or antibiotics (See paragraph 15 and 35, in particular).
WO 2010/036962 teaches a method of treating a human subject with an inhibitor of SAA, wherein the subject has chronic sepsis, wherein after treatment the subjects temperature is lowered relative to the levels of prior to the treatment (see pages 81-82, in particular). WO 2010/036962 teaches that after a first dose of the inhibitor, the subjects condition is evaluated, e.g. by measuring temperature whereby the number and strength of doses are adjusted according to the subject’s needs.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, that treatments could be provided to lower body temperature, as taught by the ‘081 publication and WO 2010/036962, in the method of treating sepsis of the ‘957 publication. For example, it would be obvious to monitor temperature, as taught by WO 2010/036962, to evaluate dosing parameters and optimize treatment schedules using the antibody SAA inhibitor of the ‘957 publication. It would be obvious to treat the patient until the sepsis and inflammation have subsequently resolved and body temperature has returned to normal for a human subject, i.e. 37 degrees C. Additionally, it would also be obvious that the sepsis patient treated in the method of the ‘957 publication would have fever, since it is a well known symptom of sepsis, and that it would be obvious to further administer secondary agents, such as NSAID, anti-infectives, or antibodies, to actively resolve the fever and return body temperature to normal for a human patient, i.e. 37 degrees C.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 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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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644