DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 2/2/26 has been entered in full. Claims 1-4, 7-8, 10-12, 14 and 16-17 are canceled. Claims 22-23, 31-32 and 36-37 are amended. New claims 41-50 are added. Claims 22-23, 25-28, 31-32, 36-37, 39 and 41-50 are pending.
Election/Restrictions
The newly added claims correspond to the following inventive groups set forth in the restriction requirement mailed on 11/7/25: claims 41 and 45-59 are part of Group IV; and claims 42-44 and 50 are linking claims linking Groups III and IV.
Applicants' election without traverse of Group IV, currently claims 31-32, 36, 41 and 45-49 in the reply filed on 2/2/26 is acknowledged. Claims 22-23, 25-27, 37, 39, 42-44 and 50 are linking claims that will be examined together with the elected invention.
Claim 28 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elections of (1) CV1-hIgG4 as the species of soluble SIRPα, and (2) atorvastatin as the species of statin, are also acknowledged. Applicants indicate the elected species read on each of the pending claims in the elected group.
Claims 22-23, 25-27, 31-32, 36-37, 39 and 41-50 are under consideration.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention is not descriptive because it is directed to “CD47 Blockade and Combination Therapies Thereof” but the claims are limited to therapy combining CD47 Blockade and a Statin. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “CD47 Blockade and Statin Combination Therapy For Reduction of Vascular Inflammation”.
---““18F-FDG PET” should be “18F-FDG PET” at page 5, ¶ 33 (5 instances); page 5, ¶ 34 (3 instances) and page 12, ¶ 51 (1 instance). Compare with page 12, ¶ 52.
Appropriate correction is required.
Claim Objections
Claims 36, 37 and 42-43 are objected to because of the following informalities:
Claim 36 is objected to for reciting “the polypeptides in Table 3”. Per MPEP § 2173.05(s), "[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claims. Incorporation by reference is a necessity doctrine, not for applicant's convenience.' Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. Ap p. & Inter. 1993)." In the instant case, each of the polypeptides of Table 3 is identified by a sequence identifier, and thus, there is a practical way to define the invention in words.
In claim 37, line 2, “…wherein the method results in a plaque area as a measure of total vessel area is reduced…” should be “…wherein the method results in a plaque area as a measure of total vessel area that is reduced…” (underlining for emphasis).
In claim 37, line 4, “…wherein the reduction in vascular inflammation results in a necrotic core as a measure of the percentage of intima area is reduced…” should be “…the reduction in vascular inflammation results in a necrotic core as a measure of the percentage of intima area that is reduced…” (underlining for emphasis).
In claims 42 and 43, line 2 of each, “18F-FDG” should be “18F-FDG”. See the specification at page 4, ¶ 23.
In claim 42, line 2, the acronym ““18F-FDG” should be accompanied by the full terminology the first time it appears, e.g., “fluorine 18 fluorodeoxyglucose (18F-FDG)”. See the specification at page 12, ¶ 52. Compare with the other acronyms in claim 42.
In claim 43, line 2, “change is vascular” should be “change in vascular”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 45-49 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 pre-AIA the applicant regards as the invention.
Claims 45, 46 and 49 each recite the limitation “the SIRPα polypeptide” in line 1. There is insufficient antecedent basis for this limitation in the claim. Specifically, each of these claims depends from independent claim 22, which does not recite a SIRPα polypeptide, and thus there is no antecedent basis for the limitation.
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above, and encompass the same indefinite subject matter.
Claim Rejections - 35 USC § 112(a), written description
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 22-23, 25-27, 31-32, 37, 39 and 41-50 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The elected invention is directed to a method of reducing vascular inflammation by administering two agents, an anti-CD47 agent and a statin. The broader linking claims, such as independent claim 22, are directed to such treatment with any type of anti-CD47 agent. While the claims are directed to a method of use of a product rather than a product per se, practicing said method of use requires a written description of the product to be used; i.e., the anti-CD47 agent. See Univ. of Rochester v G.D. Searle & Co (2004) and MPEP 2163.
The specification teaches that "the term "anti-CD47 agent" or "agent that provides for CD47 blockade" refers to any agent that reduces the binding of CD47 (e.g., on a target cell) to SIRPα (e.g., on a phagocytic cell)" with examples including "high affinity SIRPα polypeptides, and anti-CD47 antibodies or antibody fragments" (¶ 56). However, because these embodiments are only exemplary, the term "anti-CD47 agent" also broadly encompasses other structures, including other polypeptides, other antibodies, small organic molecules, inorganic compounds, nucleic acids, carbohydrates, lipids and more. Thus, the claims are directed to a genus of compounds essentially only limited by their functionality; i.e., being "anti-CD47".
The elected invention is directed to an anti-CD47 agent that is a “soluble SIRPα polypeptide”, to which dependent claim 31 is limited. CD47 and its binding partner SIRPα are both transmembrane proteins, and the soluble extracellular domain of either protein has been shown to be able to block the interaction between the two (Lin et al, 2012. Protein Expression and Purification. 85: 109-116). An isolated d1 domain of SIRPα retains the ability to block CD47 (Kauder et al, 2018. PLOS One. 13(8): 1-33). The specification teaches that “high affinity SIRPα polypeptides” that have amino acid changes in the d1 domain were known in the prior art, referencing US Patent 9,944,911 (¶ 60). The specification further provides the amino acid sequences of wild type and mutant SIRPα sequences in Table 3 of the specification. These include four wild type SIRPα variants (SEQ ID NO: 1-4); the wild type d1 domain of SIRPα (SEQ ID NO: 5); five mutant d1 domains (SEQ ID NO: 6-9l; SEQ ID NO: 12 (which are identical to SEQ ID NO: 6) and SEQ ID NO: 15); wild type d1 fused to IgG1 (SEQ ID NO: 10) or IgG4 (SEQ ID NO: 11); mutant “CV1” d1 fused to IgG4 (SEQ ID NO: 13) or IgG2 (SEQ ID NO: 14); and mutant “FD6” fused to IgG4 (SEQ ID NO: 16) or IgG2 (SEQ ID NO: 17). As compared to the wild type d1 domain of SEQ ID NO: 5, the mutant d1 domains of SEQ ID NO: 6/12, 7 and 15 each have 85% similarity; SEQ ID NO: 8 has 95.1% similarity; and SEQ ID NO: 9 has 81.2% similarity. The teachings of the prior art and the disclosure of these amino acid sequences is sufficient to provide a written description for embodiments directed to each of the SIRPα polypeptide sequences disclosed in Table 3, e.g., a protein having the amino acid sequence of SEQ ID NO: 12 or 13.
However, the claims are not limited to the disclosed sequences. Dependent claim 45 expressly includes all variants that are at least 90% identical to SEQ ID NO: 12 (mutated d1 domain), a sequence of 119 amino acids, and thus encompasses variants with up to 11 amino acid changes in combination. Claim 49 expressly includes all variants that are at least 90% identical to SEQ ID NO: 13 (mutant d1 fused to IgG4), a sequence of 346 amino acids, and thus encompasses variants with up to 34 amino acid changes. If each of these changes is present in the d1 domain of the fusion protein, this would be up to 28.6% of the protein (34 out of 119 amino acids). Furthermore, the specification teaches that the polypeptides of the invention include variants “having less than 100% sequence identity with the native sequence polypeptide” (¶ 63).
As such, the claims are directed to a genus of variants of SIRPα that retain the ability to target CD47, and the encompassed variation is without limit. The prior art appreciates that "Mutations … are generally destabilizing, and can reduce protein … fitness" and "In general, more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation" (pg 602 of Tokuriki et al, 2009, Current Opinion in Structural Biology. 19: 596-604). Thus, knowledge of the amino acid sequences of SIRPα, or an active fragment or variant thereof, is not sufficient for the skilled artisan at the time of the effective filing date to predict which combinations of mutations (substitutions, additions and deletions) will result in other variants of SIRPα corresponding in scope to the broad range of mutations encompassed by the claims, and that retain the ability to target SIRPα.
With respect to the broader genus of anti-CD47 agents that is defined by function alone (i.e., being “anti-CD47), a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; e.g., the structure of one of anti-CD47 agent does not provide predictability regarding other structures having the same functionality.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[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” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
As noted above, the genus of anti-CD47 agents encompasses any type of structure; e.g., polypeptide, antibody, nucleic acid, small molecule, carbohydrate, lipid, inorganic molecule or other. Each of these types of molecules is a subgenus encompassing multiple structures. For example, anti-CD47 polypeptides include not just SIRPα, but any other protein that interferes with the activity of CD47. However, the specification does not provide examples of anti-CD47 agents corresponding in scope to encompassed genus, and likewise does not provide examples of each of the other structural categories of agents (e.g., small molecules), which would be necessary to describe the entirety of the genus. Per MPEP 2163, "A "representative number of species" means that the species which are adequately described are representative of the entire 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). As such, the exemplary description of structures of anti-CD47 agents does not correspond that which is claimed, and therefore the specification fails to provide a written description of the genus of anti-CD47 agents.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, only a method of reducing vascular inflammation in a human subject, the method comprising administering to the subject an effective dose of an anti-CD47 agent and an effective dose of a statin, wherein the combination of the anti-CD47 agent and the statin provides for a reduction in vascular inflammation relative to the effective of either agent as a monotherapy, and wherein the anti-CD47 agent is a soluble SIRPα polypeptide that comprises the amino acid sequence of SEQ ID NO: 12, but not the full breadth of the claims, meet the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Note on Prior Art Rejection(s)
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 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 22-23, 25-27, 31-32, 36-37, 39, 41-42 and 44-50 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Leeper et al, U.S. Patent Application Publication 2018/0028651, published 2/1/18, filed 2/25/16 and claiming priority to 2/27/15 (cited on the 10/23/24 IDS). The earliest date to which the instant application claims priority is 10/28/20.
In independent claim 22, the recitation “of reducing vascular inflammation” in the preamble has been considered in the context of the entire claim, and is interpreted as an intended use for the method because it does not result in a manipulative difference between the method as defined by the steps and a prior art method teaching the same steps. See MPEP 2111.02. Furthermore, the concluding wherein clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, in claim 22 the wherein clause simply expresses the intended result (reduction in vascular inflammation relative to the effect of either agent as a monotherapy) of a process step positively recited (administering an effective dose of an anti-CD47 agent and an effective dose of a statin).
As such, claim 22 encompasses a prior art method comprising a step of administering to a human subject an effective dose of an anti-CD47 agent and an effective dose of a statin.
Leeper teaches methods “for treating or reducing atherosclerosis by administering an effective combined dose of an anti-CD47 agent and an anti-TNFα agent to increase efferocytosis of cellular components of coronary or extracardiac plaque, including the efferocytosis of apoptotic smooth muscle cells” (¶ 78). Leeper further teaches that “[i]n some other embodiments the effective combined dose of an anti-CD47 agent and an anti-TNFα agent are further combined with a third therapeutic agent, e.g., drugs useful in the treatment of atherosclerosis. Such combinations may include, without limitation, statins” (¶ 82). As such, Leeper teaches a method comprising a step of administering to a human subject a treatment that includes an effective dose of each of an anti-CD47 agent, an anti-TNFα agent, and a statin. This meets the limitations of claim 22 because it includes an effective dose of each of an anti-CD47 agent and a statin. As such, the teachings of Leeper anticipate claim 22. Furthermore, while the intended use and result of the claim 22 (reducing vascular inflammation) does not distinguish the claimed method from the teachings of Leeper, it is noted that “reducing atherosclerosis” as taught by Leeper is encompassed by “reducing vascular inflammation”, as atherosclerosis involves vascular inflammation (see the instant specification at ¶ 47; “vascular inflammation is a hallmark of the atherosclerosis disease process).
Claims 23 and 47 each further limit “the reduction in vascular inflammation” of claim 22; as such, each is directed solely to narrowing the concluding wherein clause of the parent claim. As such, the further limitation of each of claims 23 and 47 does not distinguish the claimed method from the teachings of Leeper, and these claims are therefore also anticipated by the Leeper.
Claim 25 encompasses a method of claim 22 wherein the statin is atorvastatin. Leeper further teaches that the statin may be atorvastatin (¶ 82). As such, the teachings of Leeper also anticipate claim 25.
Claim 26 encompasses a method of claim 22 wherein the method is performed in the absence of genotyping the subject for the presence of at least one 9p21 risk allele. This broadly encompasses a method wherein the method is absent performance of such genotyping because it has been performed previously on the subject. Leeper further teaches that the subject may have been “the subject has been previously diagnosed for the presence of a 9p21 risk allele” (¶ 9). As such, the teachings of Leeper also anticipate claim 26.
Claim 27 encompasses a method of claim 22 wherein the anti-CD47 agent specifically binds to CD47. Leeper further teaches that “[i]n some embodiments, a suitable anti-CD47 agent (e.g., an anti-SIRPα, antibody, etc.) specifically binds SIRPα to reduce the binding of CD47 to SIRPα” (¶ 44). As such, the teachings of Leeper also anticipate claim 27.
Claim 31 encompasses a method of claim 22 wherein the anti-CD47 agent is a soluble SIRPα polypeptide. Leeper further teaches that the anti-CD47 agent can be a high affinity SIRPα reagent (¶ 44), which can be soluble (¶ 47). As such, the teachings of Leeper also anticipate claim 31.
Claim 32 encompasses a method of claim 31 wherein the soluble SIRPα polypeptide comprises an immunoglobulin constant region. Leeper further teaches that the SIRPα polypeptide of the invention may comprise an immunoglobulin Fc region (¶ 48), which by definition is composed of antibody constant regions. As such, the teachings of Leeper also anticipate claim 32.
Claim 36 encompasses a method of claim 31 wherein the SIRPα polypeptide is selected from the polypeptides in Table 3 (pages 62-64 of the specification). This Table includes SEQ ID NO: 6, identified as the “mutant d1 domain of SIRP-alpha” (page 63). Leeper further teaches that the high affinity SIRPα reagents include those described in “PCT/US13/21937, which is hereby specifically incorporated by reference” (¶ 47). This PCT entered the national stage (371) as U.S. Application No 14/371,370, which was published as U.S. Patent Application Publication 20150071905. Thus, ‘905 is a publication of the same disclosure as the ‘937 PCT that is incorporated by reference by Leeper. The ‘905 publication teaches a “CV1 sequence” of SEQ ID NO: 10 (¶ 156), which is 100% identical to instant SEQ ID NO: 6, and thus this embodiment is incorporated by reference as part of Leeper. As such, the teachings of Leeper also anticipate claim 36.
Claims 37 and 39 each further limit the method of claim 22 by means of a further wherein clause. Each wherein clause has been fully considered in context of the entire claim and parent claim 22, but do not render the claimed method patentably distinct from a method taught by the prior art because each simply expresses the intended result of a process step positively recited. Specifically, each wherein clause simply expresses the intended result (a reduction in plaque area or vascular inflammation (claim 37) or an increased rate of efferocytosis (claim 39)) of a process step positively recited (administering an effective dose of an anti-CD47 agent and an effective dose of a statin). As such, the teachings of Leeper that anticipate parent claim 22 also meet the limitations of claims 37 and 39.
Claim 41 encompasses a method of claim 32 wherein the soluble SIRPα polypeptide is multimerized through the immunoglobulin constant region. The Fc region of an antibody is a homodimer, which is a form of multimer. As such, the teachings of Leeper that anticipate claim 32 also anticipate claim 41.
Claim 42 encompasses a method of claim 22 that comprises monitoring an indicia of vascular inflammation that is a change in CRP. Leeper further teaches “indicia appropriate for human patients” of progression of atherosclerosis that includes CRP (¶ 34). As such, the teachings of Leeper also anticipate claim 42.
Claim 45 encompasses a method of claim 22 wherein the SIRPα polypeptide comprises an amino acid sequence of SEQ ID NO: 12. Table 3 of the specification, identifies SEQ ID NO: 13 as “d1 domain of CV1-hIgG4”, and SEQ ID NO: 12 is 100% identical to instant SEQ ID NO: 6. As set forth above for claim 36, Leeper teaches a SIRPα polypeptide having 100% identity to SEQ ID NO: 6, and thus also SEQ ID NO: 12. As such, the teachings of Leeper also anticipate claim 45.
Claim 46 encompasses a method of claim 22 wherein the SIRPα polypeptide comprises a “CV1 monomer”. The specification does not provide a definition of the term “CV1 monomer”, but identifies the term as an alternate name for SEQ ID NO: 12 (see Table 3, where SEQ ID NO: 12 is identified as “d1 domain of CV1-hIgG4 or CV1 monomer”). As set forth above for claim 45, Leeper teaches a SIRPα polypeptide having 100% identity to SEQ ID NO: 12. As such, the teachings of Leeper also anticipate claim 46.
Claims 47 and 48 encompass a method of claim 46, wherein the “CV1 monomer” is fused to an Fc domain (claim 47) that is a human IgG4 Fc domain (claim 48). The ‘905 publication described above for claim 36 further teaches that the SIRPα proteins may be fusions with human IgG4 Fc chains (¶ 143). As Leeper fully incorporates the teachings of ‘905, the teachings of Leeper also anticipate claims 47 and 48.
Claim 49 encompasses a method of claim 22, wherein the SIRPα polypeptide comprises an amino acid sequence of SEQ ID NO: 13, which is identified in Table 13 as “d1 domain of CV1 fused to the human IgG4 Fc domain (i.e., CV1-hIgG4)”. The ‘905 publication described above for claims 36, 47 and 48 further teaches a CV1-hIgG4 fusion protein having the amino acid sequence of SEQ ID NO: 41 (¶ 190), and this sequence is 100% identical to instant SEQ ID NO: 13 . As Leeper fully incorporates the teachings of ‘905, the teachings of Leeper also anticipate claim 49.
Claim 50 encompasses a method of claim 22 wherein the anti-CD47 agent and the statin are administered separately. The teachings of Leeper that are directed to administration of an anti-CD47 agent and a statin are referred as “combinations” (¶ 82), which is combination therapy. Leeper further teaches that combination therapy of the invention includes sequential administration (¶ 53), which is encompassed by “separately” as recited in claim 50. As such, the teachings of Leeper also anticipate claim 50.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 43 is rejected under 35 U.S.C. 103(a) as being unpatentable over Leeper et al, U.S. Patent Application Publication 2018/0028651, published 2/1/18, filed 2/25/16 and claiming priority to 2/27/15 (cited on the 10/23/24 IDS), as applied to claim 42 above, and further in view of U.S. Patent Application Publication 2017/0325697, published 11/16/17, filed 5/11/17 and claiming priority to 5/12/16.
Claim 43 limits the method of claim 42 to one wherein the indicia of vascular inflammation is a change in vascular 18F-FDG uptake. The instant specification indicates that 18F-FDG is fluorine 18 fluorodeoxyglucose (page 12, paragraph 52). As such, claim 43 encompasses a prior art method comprising a step of administering to a human subject an effective dose of an anti-CD47 agent and an effective dose of a statin, and further wherein the method comprises monitoring an indicia of vascular inflammation that is a change in vascular 18F-FDG (fluorine 18 fluorodeoxyglucose) uptake. The teachings of Leeper that anticipate parent claim 42 are set forth above. While as described above for claim 42, Leeper teaches indicia for progression of atherosclerosis, Leeper does not teach that such indicia include a change in vascular 18F-FDG.
Zaman teach a probe device and method “to provide for improved atherosclerosis detection and evaluation, even in early atherosclerosis” and that uses “18F-fluorodeoxyglucose (18F-FDG), a marker of vascular inflammation, to detect and characterize atherosclerotic plaque” (¶ 7). Zaman further teaches that “Vulnerable atherosclerotic plaque is composed of a thin fibrous cap, a large lipid pool, and a large number of macrophages. These macrophages uptake an increased amount of 18F-fluorodeoxyglucose (18F-FDG) glucose molecule, compared to normal arterial tissue” and that “the probe can detect vulnerable atherosclerotic plaque with high sensitivity and accuracy, unlike currently available imaging modalities” (¶ 37).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method comprising a step of administering to a human subject an effective dose of each of an anti-CD47 agent, an anti-TNFα agent, and a statin, and monitoring an indicia of atherosclerosis (which is a form of vascular inflammation), that is taught by Leeper, and modify it to use vascular 18F-FDG update as the monitoring indicia. The person of ordinary skill in the art would have been motivated to make such a change in order to take advantage of the improvements (high sensitivity and accuracy) in monitoring atherosclerosis taught by Zaman. The person of ordinary skill in the art would have had a reasonable expectation of success in employing the modification because the treatment and monitoring technique are taught for use with the same disease (atherosclerosis). This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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