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 .
DETAILED ACTION
Status of the Claims
Claims 1-17 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record to the extent that each was provided.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 1 and 4-17 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claims contain 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(s), at the time the application was filed, had possession of the claimed invention. Specifically, claim 1 recites "an annexin V agent".
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to MPEP §2163. In particular, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plan for obtaining the chemical invention claimed. An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "functional characteristics when coupled with a known or disclosed correlation between function and structure..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106). Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP §2163. However, if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP §2163.
The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886, 1892 (CAFC 2004). A description of what a material does, rather than of what it is, usually does not suffice to provide an adequate written description of the invention. Univ. of Cal. V. Eli Lilly, 119 F.3d 1559, 1568 (Fed. Cir. 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. See Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011). Furthermore, to the extent that a functional description can meet the requirement for an adequate written description, it can do so only in accordance with PTO guidelines stating that the requirement can be met by disclosing "sufficiently detailed, relevant identifying characteristics," including "functional characteristics when coupled with a known or disclosed correlation between function and structure." Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1427, 1432 (DC WNY 2003).
A more recent Federal Circuit decision, Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describes how when an antibody is claimed 35 U.S.C. § 112(a) requires adequate written description of the antibody itself not just a description of the sequence to which the antibody binds. See Amgen, 872 F.3d at 1378-79.
"It is 'not a question of whether one skilled in the art might be able to construct the patentee's device from the teachings of the disclosure ....Rather, it is a question whether the application necessarily discloses that particular device.'" Martin v. Mayer , 823 F.2d 500, 505 (Fed. Cir. 1987), quoting Jepson v. Coleman, 314 F.2d 533, 536 (CCPA 1963)). Here, because the specification lacks a description of structural features required to exhibit the recited property or a description of the structural features of a pharmaceutical composition "configured such that" it will exhibit the recited property, the specification does not support a finding that the particular composition is necessarily disclosed.
In paragraphs [0025] and [0097], applicants mention a narrow set of functional analogs or variants of annexin v (A5), but it is clear that the term "an annexin V agent" is not limited to only the variants discussed those portions of the specification. Additionally, applicants have failed to provide any further description of the genus of "an annexin V agent" as recited in instant claim 1 that would provide adequate written description of the compounds encompassed by the claim. Adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties. Applicants provide no direction as to what subset of variants or derivatives out of all possible compounds and modification technologies that exist in the art would possess the required properties and be useful as "an annexin V agent" in the invention. Furthermore, the structures of the particular variants disclosed in the specification are not representative of other species of derivatives, for example polymer conjugates, antibodies, or degradation products, encompassed by the genus. In the present case, other than the specific compounds mentioned in the specification, the disclosure fails to describe the claimed compounds in a manner that complies with the written description requirement of 35 USC § 112(a).
Applicant is alerted that "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." AriadPharms., Inc. v. EliLilly & Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010). A "generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus." Id. at 1349. “[M]erely drawing a fence around a perceived genus is not a description of the genus.” AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014). “One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.” Id. “Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” Id.
Claim Rejections - 35 USC § 112(b) or (pre-AIA ) 35 USC § 112 (2nd Par.)
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.
Claim 13 is 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.
Claim 13 recites the limitation "wherein the subject has less than 10,000 viral copies per milliliter of blood". The antecedent basis for this limitation in the claim is not clear because claim 1, from which claim 13 depends does not recite a virus at all. Since the only mention of a number of viral copies occurs in the context of HIV infection (see instant par. [0010]), the claim does not appear to provide sufficient antecedent basis for this limitation, as claim 1 does not require viral infection at all, let alone HIV infection specifically. See MPEP § 2173.05(e). Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-11 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over BLANKENBERG (US 2017/0202914; Pub. Jul. 20, 2017; on IDS) in view of BIRGE (Birge, R. B., et al. Cell Death Differ. (2016), 23; 962-978) and KELLEHER (Kelleher, R. J., et al. Cancer Immunol. Res. (2015), 3(11); 1269-1278; on IDS).
Blankenberg discloses methods of using annexin V to block tumor induced immunosuppression (title; abstract; [0009]). Blankenberg teaches annexin V is a well-tolerated therapeutic and diagnostic agent with no reported adverse events ([0009], [0129]). Blankenberg teaches annexin V blocks phosphatidylserine (PS) on tumor cells, and thereby disrupts an undesirable interaction between tumor cells and immunoregulatory cells ([0005]-[0009], [0070]). Blankenberg teaches annexin V can reverse PS induced immunosuppression caused by tumors ([0129]). Both high and intermediate levels of PS on tumor cells and tumor associated antigen (TAA) reactive T lymphocytes induce the transition of monocytes/macrophages (MDs) from an active to a tolerogenic phenotype ([0130]-[0131]). Tolerogenic MDs, induce the development of tumor-specific T-regs (T cell, regulatory); cells that actively suppress CD8+ (cytotoxic) T cells (CTLs), leading to immunosuppression ([0131]). Blankenberg teaches delivery of annexin V via i.v. or i.p. injection (i.e., parenteral administration) ([0008], [0010], [0012], [0088]).
While Blankenberg teaches that annexin V blocks PS, which suppresses CTLs ([0007], [0038]-[0039], [0131]), Blankenberg does not expressly teach treating CTL exhaustion with annexin V.
Birge reports that phosphatidylserine (PS) is a global immunosuppressive signal in infectious disease and cancer (title; abstract). Birge teaches that exposed PS is an immunosuppressive signal, and agents targeting PS could have significant value in cancer and infectious disease therapeutics (abstract; p. 967, 2nd col.). Birge teaches that strategies that inhibit PS signaling thereby preventing PS-mediated immune suppression in tumors are attractive (p. 972, 2nd col.). Birge teaches that preclinical studies with annexin A5 (AnxA5; i.e., annexin V), a natural ligand for PS, support this idea (p. 972, 2nd col.; see also the par. bridging pgs. 972-973).
"With respect to the role of AnxA5 in infectious diseases, the infectivity of HIV-1 for human macrophages is decreased in the presence of AnxA5.106 Moreover, PS and a non-phospholipid component of the Hepatitis B virus (HBV) envelope are involved in AnxA5 binding and HBV infection.110 The disruption by AnxA5 of PS-mediated signals might be utilized for therapeutic interventions in a multitude of infectious diseases." (p. 973; 1st col.)
Birge teaches T-cell exhaustion, which is a defective T-cell response found in many chronic infections and in cancer, is an active area of research (p. 967, 2nd col.).
Kelleher reports on PS-dependent arrest in the T cell signaling cascade (title; abstract). Kelleher teaches that inhibition of T cell activation was causally linked to PS, and blockade of PS inhibits this PS-induced signaling arrest (abstract). Kelleher links this T cell arrest with T cell exhaustion in chronic infections and cancer (p. 10, top par.; p. 11, 1st full par.). Kelleher concludes that targeting PS is a strategy to prevent T cell arrest (p. 11).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have treated a subject with CTL exhaustion by administering annexin V. One would have been motivated to do so since annexin V is known to bind an block PS, which is a cause of immunosuppression, including CTL exhaustion. Further, Birge specifically teaches CTL exhaustion as an area of research, and Kelleher teaches targeting PS can reverse T cell arrest.
Regarding claims 3-4, Blankenberg teaches human annexin V ([0044], [0046], [0074]), as well as administration to humans ([0010], [0032], [0037]).
Regarding claims 5-6, Birge teaches the infectivity of HIV for human macrophages is decreased in the presence of AnxA5, and directly suggests the use of annexin V for therapeutic interventions in a multitude of infectious diseases such as HIV, and specifically teaches HIV-1 (p. 973; 1st col.; Table 1b; P. 974, 2nd col.). As there are only two types of HIV (HIV-1 and HIV-2) an artisan in this field readily envisions treatment of either type based on Birge.
Regarding claims 7-8, Birge teaches the advantages of using AnxA5 in HIV infection (p. 973; 1st col.; Table 1b; P. 974, 2nd col.), and it would have been prima facie obvious to one of ordinary skill in the art to have monitored an HIV-infected subject for signs of infection or viral load following treatment. Likewise, it would have been obvious to one seeking to treat CTL exhaustion in a subject to monitor the subject for indicia of CTL exhaustion. One would monitor these outcomes as a matter of routine practice in order to asses the effectiveness of the treatment regimen.
Regarding claim 9, Blankenberg teaches the effective dose of annexin V in a human is from up to about 50 µg/kg to up to about 20 mg/kg ([0010]).
Regarding claim 10, Blankenberg teaches the annexin V is administered in a manner that provides for prolonged blood clearance, for example where the half-life of the protein in circulation is at least about 1 hour ([0012]).
Regarding claim 11, Blankenberg teaches combining annexin V with other therapeutic agents ([0011], [0023], [0064], [0071], [0076], [0087]).
Regarding claims 14-16, these claims recite the intended outcome of the positively recited method steps. MPEP § 2111.04(I) 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. The intended results recited in claims 14-16 are present in wherein clauses, which do not add any structural features to the claims. Regarding wherein clauses and intended use, the MPEP states, "Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. The following are examples of language that may raise a question as to the limiting effect of the language in a claim:
(A) statements of intended use or field of use,
(B) “adapted to” or “adapted for” clauses,
(C) “wherein” clauses…"
(D) “whereby” clauses.
This list of examples is not intended to be exhaustive. See also MPEP § 2111.04." See MPEP § 2103(I)(C).
Regarding claim 17, the CTLs would be HIV specific when treating CTL exhaustion in an HIV-infected subject, absent evidence to the contrary.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over BLANKENBERG in view of BIRGE and KELLEHER, and further in view of NZUZA (Nzuza, S., et al. J. Endocrinol. Metab. (2017), 7(4); 103-116), as evidenced by YENI (Yeni, P., J. Hepatol. (2006), 44; S100-S103).
The teachings of Blankenberg, Birge, and Kelleher are presented supra, and are incorporated herein.
Blankenberg does not teach treating a subject with a combination of highly active antiretroviral therapy (HAART) and annexin V.
Nzuza reports on HAART in HIV therapy (title; abstract). Nzuza teaches that the use of HAART has extremely enhanced the clinical outcome of HIV with a decrease in mortality and morbidity (abstract). Nzuza teaches that currently available once-daily fixed-dose combination HAART therapies include tenofovir/emtricitabine/efavirenz as the gold standard of care (section entitled “Pharmacological Interventions”).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have treated a subject being treated with HAART with annexin V. One would have been motivated to do so since HAART is the gold standard of care for HIV infection and since it enhances the clinical outcome of HIV by decreasing mortality and morbidity. Further, one would have a high expectation of success since Blankenberg teaches combining annexin V with other therapeutic agents ([0011], [0023], [0064], [0071], [0076], [0087]).
Regarding claim 13, most HIV patients who respond properly to HAART treatment have viral loads of less than 10,000 copies per milliliter of blood. For example, Yeni reports on HAART treatment in HIV (title; abstract). Yeni teaches that HAART has dramatically decreased the mortality rate of HIV-infected patients since it became available in 1996 (abstract, p. S100). Yeni teaches that HAART maintains HIV-RNA copy number at an undetectable level (<50 copies per ml) (p. S100). Thus, treating a patient on HAART therapy would generally meet the limitation of claim 13.
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 obviousness-type 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); and 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
US Patent 11,253,568
Claims 1-17 are non-provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-13 of US Patent 11,253,568 in view of Birge, and Kelleher. Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '568 claims anticipates or renders obvious that of the instant claims. The difference between the two claim sets is that the '568 claims recite increasing the immune response to a tumor. However, Birge and Kelleher teach that annexin V is suitable to treat both CTL exhaustion, such as that occurring in chronic infectious disease (e.g., HIV) and cancer. Thus the scope of the instant claims is an obvious variation of the '568 claims.
Conclusion
Claims 1-17 are rejected. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kevin S Orwig whose telephone number is (571)270-5869. The examiner can normally be reached Mon.-Fri. 7AM-4PM (with alternate Fridays off). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached Mon.-Fri. at (571)272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of applications may be obtained from Patent Center. Patent Center is available to registered users regarding unpublished application information. To file and manage patent submissions, visit: https://patentcenter.uspto.gov and for more information visit https://www.uspto.gov/patents/apply/patent-center and https://www.uspto.gov/patents/docx. The fax number for the organization where this application is assigned is (571) 273-8300. For additional questions, contact the Electronic Business Center (EBC) at (866) 217-9197. If you would like assistance from a USPTO Customer Service Representative, call (800) 786-9199 or (571) 272-1000.
/Kevin S Orwig/Primary Examiner, Art Unit 3991