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 .
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.
DETAILED ACTION
Claims 1-26 are pending and under examination.
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 3-6, 10 and 15 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.
Claim 1 recites “a method of inhibiting microvascular endothelial cell injury and/or thrombus 5 formation in a subject suffering from thrombotic thrombocytopenic purpura (TTP) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody effective to inhibit MASP-2-dependent complement activation.”
Dependent claim 3 recites “The method of Claim 1, wherein the MASP-2 inhibitory agent is an anti-MASP-2 antibody, or fragment thereof.”
Considering claim 1 in the light of the teachings of the instant specification and the ordinary use of the phrase “a antigen X inhibitory antibody" the skilled artisan would understand claim 1 to be drawn to a method comprising administering an anti-masp-2 inhibitory antibody to a subject.
By this interpretation claim 3 is an improper dependent claim because claim 1 is drawn to a masp-2 inhibitory antibody while claim 3 expands the method of claim 1 to include methods employing fragments of anti-masp-2 antibodies.
However, a more obtuse1 but nonetheless possible interpretation of claim 1 is possibly suggested by the language of claim 3 in that claim 3 could be understood to imply that claim 1 encompasses something other than anti-masp-2 antibodies in its breadth, i.e., that the “MASP-2 inhibitory antibody effective to inhibit MASP-2-dependent complement activation” of claim 1 encompasses something more than inhibitory antibodies that bind masp-2.
Amending claim 1 to recite, “administering…a masp-2 inhibitory antibody or a masp-2-binding fragment thereof, said antibody or fragment thereof effectively inhibiting masp-2-dependent complement activation” would address this aspect of the rejection.
All that said, for the remainder of this office action it will be assumed for examination purposes that claim 1 is drawn to a method employing an antibody that binds masp-2 and inhibits masp-2-dependent complement activation.
Moreover, claims 3-6 which depend from claim 1 also refer to “the masp-2 inhibitor agent;” however, claim 1 does not generically recite administering “a masp-2 inhibitory agent,” rather it recites administering “a masp-2 inhibitory antibody.” Thus, “agent” lacks antecedent basis in claim 1 in that it is not clear if agent is another term for the antibody of claim 1 or for some other masp-2 inhibitory agent. Amending claims 3-6 to recite “wherein the masp-2 inhibitory antibody…” would address this aspect of the rejection.
Claim 10 recites “A method of treating a subject suffering from TTP...comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation, 10wherein the administration of the MASP-2 inhibitory agent is administered to the subject via an intravenous catheter or other catheter delivery method…wherein the composition…is administered for a first time period in the absence of plasmapheresis.”
It would be unclear to the skilled artisan precisely what is meant by the phrase “for a first time period in the absence of plasmapheresis” as it is used in this claim.
Does this phrase imply that to practice the claimed method there must be a second time period that includes treatment with a masp-2 inhibitory agent + plasmapheresis? If not, then how could this claim be said to further limit the subject matter of base claim 7, i.e., how could this claim be said to be a proper dependent claim?
Moreover, does the use of the phrase “first time period” imply that there cannot be any time period before this first time period? For example, if someone begins treating a patient with plasmapheresis, then stops plasmapheresis and treats with a masp-2 inhibitory agent, and then after some time continues plasmapheresis treatment are they practicing the invention of claim 10?
Claim 15 recites,
“A method of treating a subject suffering from…TTP...comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation, 10wherein the administration of the MASP-2 inhibitory agent is administered to the subject via an intravenous catheter or other catheter delivery method, wherein the composition comprising the masp-2 inhibitory agent is administered via a catheter for the first time period, further comprising administering the composition comprising the MASP-2 inhibitory agent for a second time period, wherein the composition is administered subcutaneously during the second time 20 period, and further comprising periodically determining the level of at least one complement factor, wherein the determination of a reduced level of the at least one complement factor in comparison to a standard value or a healthy subject is indicative of the need for continued treatment with the composition.”
The term "standard value" is a relative term which renders the claim indefinite. The term "standard value" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The skilled artisan cannot ascertain where the metes and bounds of the rejected claims lie given the alternative ways the language of the claims could be understood by different persons of skill in the art as set forth above.
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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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 3 and 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As described above claim 1 is drawn to a masp-2 inhibitory antibody while claims 3 and 4 expand the masp-2 inhibitory agent to include a fragment of an anti-masp-2 antibody.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-8, 10, 16-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schwaeble et al. (2007/0172483, cited on an IDS).
Schwaeble teaches a method of treating a subject suffering from autoimmune thrombotic thrombocytopenic purpura (TTP) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation, 10 wherein the administration of the MASP-2 inhibitory agent is administered to the subject via an intravenous catheter or other catheter delivery method (see paragraph 268 and claim 48). Schwaeble teaches the MASP-2 inhibitory agent can be an anti-masp-2 chimeric, humanized or human antibody that binds to a portion of SEQ ID NO: 6 and has reduced effector functions (see paragraphs 316-3212 and claim 9).
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 of this title, 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.
Claims 1-14, 16-21, 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Schwaeble et al. (2007/0172483) in view of and Plaimauer et al. (Thromb Haemost 2011; 9: 936–44) and Bobbio-Pallavicini et al. (Eur J Haematol 1994: 52: 222-226)(all cited on an IDS).
Schwaeble teaches a method of treating a subject suffering from autoimmune thrombotic thrombocytopenic purpura (TTP) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation, 10 wherein the administration of the MASP-2 inhibitory agent is administered to the subject via an intravenous catheter or other catheter delivery method (see paragraph 268 and claim 48). Schwaeble teaches the MASP-2 inhibitory agent can be an anti-masp-2 chimeric, humanized or human antibody that binds to a portion of SEQ ID NO: 6 and has reduced effector functions (see paragraphs 316-3212 and claim 9).
However, Schwaeble does not explicitly teach a method of treating TTP wherein the TTP patient tests positive for the presence of an inhibitor of ADAMTS13 comprising administering a MASP-2 inhibitory agent and further comprising administering an immunosuppressant (claim 9); a method of treating TTP wherein the TTP patient tests positive for the presence of an inhibitor of ADAMTS13 comprising administering a MASP-2 inhibitory agent and further comprising ADAMTS-13 (claim 11); or for a method of treating TTP comprising administering a MASP-2 inhibitor agent and further comprising treating the patient with plasmapheresis (claim 12); or for a method of treating TTP comprising administering a MASP-2 inhibitor agent and further wherin the masp-2 inhibitor agent is administered in the presence of plasmapheresis (claim 13); or administering a masp-2 inhibitor agent via a catheter for a first time period and further administering the MASP-2 inhibitory agent subcutaneously for a second time 20 period (claim 14); or treating refractory TTP by administering a MASP-2 inhibitory agent (claims 20-26).
Plaimauer teaches the congenital form of TTP is exceedingly rare compared to acquired idiopathic TTP mediated by autoantibodies directed against ADAMTS13. Plaimauer further teaches plasma exchange is the treatment of choice in acquired TTP and is considered to remove circulating inhibitory antibodies whilst replenishing ADAMTS13. Additionally, Plaimauer describes that Plasma-refractory and multiple relapsing TTP patients may benefit from additional immunosuppressive treatment such as corticosteroids or other agents like rituximab or cyclosporine (see bridging paragraph on page 936 – page 936-37 bridging paragraph and page 942, right column).
With respect to this last teaching of Plaimauer in particular, Bobbio teaches TTP patients can be refractory to plasma exchange for a variety of reasons including that it is given intermittently rather than daily. Bobbio further teaches the immunosuppressive agent vincristine can be used to treat TTP patients refractory to conventional therapy (see page 225, left col., 3rd paragraph of Discussion).
With respect to treating TTP wherein the TTP patient tests positive for the presence of an inhibitor of ADAMTS13 comprising administering a MASP-2 inhibitory agent and further comprising administering an immunosuppressant or ADAMTS13, firstly, as taught by Plaimauer autoimmune TTP is caused by anti-ADAMTS13 (see page 936, right col., starting at line 9). Thus, in the course of attempting to determine if a given patient has autoimmune TTP as compared to, e.g., atypical HUS, the ordinarily skilled artisan would have necessarily determined if the patient tests positive for an inhibitor of ADAMTS13 prior to firmly diagnosing the patient with autoimmune TTP.
Secondly, as taught by Plaimauer autoimmune TTP mediated by anti-ADAMTS13 can be treated with immunosuppressive agents or by administering ADAMTS13. Thus, it would have been prima facie obvious to one of ordinary skill in the art that autoimmune TTP mediated by anti-ADAMTS13 could be treated by administering an anti-masp-2 inhibitor such as an anti-masp-2 monoclonal antibody, and by further administering a second agent known to treat autoimmune TTP such as an immunosuppressant or ADAMTS13.
As pointed out in MPEP 2144.06 (I), "It is prima facie obvious to combine two
compositions each of which is taught by the prior art to be useful for the same purpose, in
order to form a third composition to be used for the very same purpose…. [T]he idea of
combining them flows logically from their having been individually taught in the prior art."
In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
This rationale is also consistent with KSR Exemplary Rationale (A) (see MPEP 2141 (III)):
Combining prior art elements (administration of anti-masp-2 antibody to treat autoimmune TTP with administration of an immunosuppressant or ADAMTS13 to treat autoimmune TTP) according to known methods to yield predictable results (treatment of autoimmune TTP).
With respect to treating autoimmune TTP by administering a MASP-2 inhibitory agent and further comprising treating the patient with plasmapheresis (claim 12), or treating autoimmune TTP by administering a MASP-2 inhibitory agent in the presence of plasmapheresis, as taught by Plaimauer et al. and Bobbio et al. plasma exchange, a.k.a. plasmapheresis, is the treatment of choice for autoimmune TTP.
Thus, it would have been prima facie obvious to one of ordinary skill to attempt to treat autoimmune TTP with plasmapheresis, and if such a treatment did not succeed, then to treat said patient with an anti-masp-2 inhibitor such as an anti-masp-2 monoclonal antibody (claim 12). Likewise, it alternatively would ahev been obvious to one of ordinary skill in the art to treat autoimmune TTP with the combination of plasmapheresis + an an anti-masp-2 monoclonal antibody, each of these forms of treatment being taught to treat the disease.
As pointed out in MPEP 2144.06 (I), "It is prima facie obvious to combine two
compositions each of which is taught by the prior art to be useful for the same purpose, in
order to form a third composition to be used for the very same purpose…. [T]he idea of
combining them flows logically from their having been individually taught in the prior art."
In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
This rationale is also consistent with KSR Exemplary Rationale (A) (see MPEP 2141 (III)):
Combining prior art elements (administration of anti-masp-2 antibody to treat autoimmune TTP with administration of plasmapheresis to treat autoimmune TTP) according to known methods to yield predictable results (treatment of autoimmune TTP).
Similarly, with respect to treating a subject suffering from refractory TTP by administering an anti-masp-2 antibody, as described by Plaimauer et al. and Bobbio et al., when a TTP patient fails to respond to plasmapheresis one should attempt to treat the disease with an immunosuppressive / immunomodulatory agents such a rituximab, cyclosporine or vincristine. It would have been obvious to one of ordinary skill in the art that treatment with a masp-2 inhibitor such as an anti-masp-2 antibody represents another alternative treatment for plasmapheresis refractory TTP patients, said treatment yielding the predictable result of treating TTP.
With respect to administering a masp-2 inhibitor agent via a catheter for a first time period and further administering the MASP-2 inhibitory agent subcutaneously for a second time 20 period, Schwaeble teaches masp-2 inhibitory agents can be administered by a variety of routes including intravenous and subcutaneous (see paragraphs 428-432).
It would have been obvious to one of ordinary skill in the art that any combination of routes could be used to achieve the same predictable result of introducing a masp-2 inhibitory protein, such as an anti-masp2 antibody, into the patient's circulation. That said, one reason the skilled artisan would have been motivated to administer an anti-masp2 antibody via a catheter for a first time period and then subcutaneous during a second time period is because, while the initial administration may occur in a clinical setting equipped for catheterization, subsequent administrations may occur in a non-clinical setting, for example in the patient’s home.
In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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 3, 4 and 7-26 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 enablement requirement because the specification, while being enabling for practicing methods which recite administering a masp-2 inhibitory agent which is an anti-masp-2 antibody, does not reasonably provide enablement for practicing the methods as claimed with any MASP-2 inhibitory agent or with any fragment of a MASP-2 antibody, or for practicing the method of claims 15 and 22 for the additional reasons given below.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claims 7 and 16 are representative of the rejected claims: methods of treatment comprising administering an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation or administering any fragment of an anti-masp-2 antibody.
The instant specification teaches and exemplifies the production of anti-MASP-2 antibodies and MASP-2 inhibitory peptides capable of inhibiting MASP-2-dependent complement activation.
However, the knowledge in the art for practicing a method of inhibiting MASP-2-dependent complement activation in a subject suffering from TTP comprising administering to the subject a composition comprising an amount of any MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation is low.
The MASP-2 inhibitory agent recited in the instant claim, given its broadest reasonable interpretation consistent with the instant specification encompasses in its breadth treatment methods employing, e.g., MASP-2 expression inhibitors, soluble MASP-2 receptors and MASP-2 small molecule inhibitors, see page 99-100 bridging paragraph – page 114.
As to practicing the claimed methods of treatment with the various expression inhibitors that would target MASP-2 described in the instant specification, other than generically describing how to make a variety of MASP-2 expression inhibitors the instant specification does not exemplify treatment of a subject suffering from TTP with the variety of MASP-2 expression inhibitors contemplated. This is important because the primary challenge in the nucleic acid-based expression inhibitor art is understanding how a particular nucleic acid i) distributes throughout the body ii) gets picked up by the target cell before being degraded by extracellular exonucleases, and iii) gets to the nucleus or the cytoplasm of the target cell and gains access to targeted DNA or mRNA (see Shoji et al., Current Pharmaceutical Design, 2004, 10, 785-796, e.g., Introduction on pages 785-86; Figures 1 and 2 and Conclusion on page 793 as well as Khan et al., J Biomed Sci 2003;10:457-467, page 465, both cited on an IDS). Based on the teachings of the art highlighted above it is evident that the skilled artisan would have to undertake a basic science research project to determine what type of nucleic acid can be used to treat a subject suffering from TTP comprising administering an amount of a nucleic-acid based MASP-2 expression inhibitor. Such a research endeavor would require undue experimentation.
As to soluble MASP-2 receptors, it would not be clear to the skilled artisan how they are supposed to go about making such a molecule given the absence of any substantive teachings in this regard. Moreover, the skilled artisan would not know how to use the natural ligands of MASP-2 such as MBL and C4, which could be considered soluble MASP-2 receptors, to inhibit MASP-2-dependent complement activation.
As to using any fragment of a MASP-2 antibody to inhibit MASP-2-dependent complement activation the skilled artisan would be quite unsure about their ability to inhibit the lectin pathway of complement with, e.g., any fragment of the antibody Fc domain. While the skilled artisan might imagine the classical pathway of complement activation could be influenced by administering certain antibody Fc fragments, far more than routine experimentation would be required to determine how such as fragment can also inhibit MASP-2-dependent complement activation.
As to small molecule inhibitors of MASP-2, the specification teaches the skilled artisan to create a library of potential MASP-2 inhibitors using the MASP-2 crystal structure and molecular modeling techniques known in the art and then test said inhibitors in a MASP-2 activity assay (see instant specification page 108, 2nd paragraph – page 109, 1st paragraph).
However, the task of making a non-peptidic organic inhibitor of a protein to protein interaction, such as the MASP-2-MBL interaction, is largely unexplored territory in the therapeutic arts, and presents a major research challenge (see Ziwei Huang, Pharmacol Ther. 2000 Jun;86(3):201-15, in particular page 202, left and right columns of the Introduction and the Conclusion section bridging pages 212-213, cited on an IDS). Moreover, even by 2007 identifying small molecule inhibitors of protein-protein interfaces with specificities, affinities and ADME useful for in vivo applications was still a highly uncertain endeavor requiring far more than routine experimentation (see, e.g., Wells et al., Nature. 2007 Dec 13;450(7172):1001-9, Introduction and “Prospects and challenges for drug discovery” on page 1008, cited on an IDS).
An additional issue with respect to claims 15 and 22 is as follows: claim 15 is directed to a method of treating TTP with a masp-2 inhibitory agent, said method comprising administering “the MASP-2 inhibitory agent…via a catheter for a first time period, further comprising administering the composition comprising the MASP-2 inhibitory agent for a second time period, wherein the composition is administered subcutaneously during the second time 20 period, and further comprising periodically determining the level of at least one complement factor, wherein the determination of a reduced level of the at least one complement factor in comparison to a standard value or a healthy subject is indicative of the need for continued treatment with the composition.”
The specification instructs:
“In one embodiment, the MASP-2 inhibitor (e.g., an anti-MASP-2 antibody) is administered to a subject with refractory TTP on a chronic basis, over a time period of at least two weeks or longer via subcutaneous or other parenteral administration. Administration may be repeated as determined by a physician until the condition has been resolved or is controlled.
In some embodiments, the method further comprises determining the level of at least one complement factor (e.g., C3, C5) in the subject prior to treatment, and optionally during treatment, wherein the determination of a reduced level of the at least one complement factor in comparison to a standard value or healthy control subject is indicative of the need for continued treatment with the MASP-2 inhibitory agent.”
The knowledge in the art prior to applicant’s earliest effective priority date correlating low levels of complement factors with the need for continued treatment with a masp-2 inhibitory agent in a patient with TTP was low.
The skilled artisan would have little idea from the teachings of the instant specification how they are to go about monitoring the effectiveness of the methods of claims 15 and 22 by “periodically determining the level of at least one complement factor, wherein the determination of a reduced level of the at least one complement factor in comparison to a standard value or a healthy subject is indicative of the need for continued treatment with the composition.” The art teaches various complement factors are elevated during the acute phase of TTP and diminish when the patient recovers (see, e.g., Reti et al., Journal of Thrombosis and Haemostasis, 10: 791–798, Discussion Section 1st and 2nd paragraphs, cited on an IDS). Notably, while diminished levels of C3 were observed in a minority of patients during the acute phase of TTP (2/13, see Reti at page 796, right col., 1st full paragraph) this observation would not be sufficient to allow the skilled artisan to monitor the efficacy of masp-2 inhibitor treatment in most TTP patients. Moreover, while Reti notes that Ruiz-Torres et al. (Thromb Haemost 2005; 93: 443-52, cited on an IDS) showed lowered levels of C3 during the acute phase of TTP, the teachings of Ruiz-Torres would not have taught the skilled artisan how to successfully monitor the treatment of TTP with a masp-2 inhibitor by measuring changes in C3 values. Far more than routine experimentation would be required of the skilled artisan to determine if the slight increases in C3 levels seen in Table 1 of Ruiz-Torres when TTP patients are in remission are more than just random fluctuations, i.e., if they are statistical significance. Additionally, even setting aside C3 levels, as described by Reti production of other complement factors increases during the acute phase of TTP and the instant specification provides no direction or guidance as to which species of the large genus of complement factors can be used to monitor the therapeutic efficacy of masp-2 inhibition. Thus, it is unclear which complement factor(s) will be indicative of a need for increased masp-2 antagonism when present at a reduced level, and undue experimentation would be required of the skilled artisan to determine which complement factors, if any, are correlated with a need for increased masp-2 antagonism in TTP.
Conclusion
The instant claims encompass an invention of tremendous breadth, and essentially call for trial and error by the skilled artisan to begin discovering how to make and use the claimed invention without assisting the skilled artisan in such an endeavor, which is insufficient to constitute adequate enablement.
As put forth in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), “[i]f mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to ‘inventions’ consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the ‘inventor’ would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
Similarly, a patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 1001,(CAFC 1997), the court held: “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure”. Further, “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”.
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
The following is a quotation of the first paragraph of 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 3, 4 and 7-26 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by functional characteristic, such as its ability to inhibit MASP-2 dependent complement activity, without any known or disclosed correlation between that function and the structure of the antagonist, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995).
In the instant case, with respect to establishing possession of methods of treatment employing the genus of MASP-2 inhibitory agents, neither the instant specification nor the knowledge in the art sufficiently establish that applicant was in possession of the claimed invention as of their date of invention.
The MASP-2 inhibitory agent of the instant claims given their broadest reasonable interpretation consistent with the instant specification encompasses in their breadth not only anti-MASP-2 antibodies and MASP-2 inhibitory peptides but also, e.g., small molecule inhibitors of MASP-2 as well as nucleic acid based MASP-2 inhibitory agents as described in the preceding Section.
As to nucleic acid-based MASP-2 inhibitory agents, the instant specification does not provide adequate written description of the broad genus of nucleic acid-based MASP-2 inhibitory agents capable of treating a subject suffering TTP because relevant identifying characteristics for said inhibitory agents, such as the particular structural or other physical and/or chemical characteristics that are critical for their function, i.e., inhibiting MASP-2-dependnet complement activation, are not disclosed. The instant specification does not provide sufficient direction or guidance as to the nucleotide structure common to the different species of nucleic acid-based MASP-2 inhibitory agents that will promote their distribution to the appropriate bodily tissue/organ or ensure that they will be picked up by the target cell before being degraded by extracellular exonucleases, and gain access to the nucleus or the cytoplasm of the target cell, essentially for the reasons stated above.
Moreover, the instant specification does not provide adequate written description of the broad genus of small molecule MASP-2 inhibitory agents capable of treating a subject suffering from TTP because relevant identifying characteristics for said small molecules, such as the particular structural or other physical and/or chemical characteristics that are critical for their function, i.e., inhibiting MASP-2-dependent complement activation are not disclosed. Furthermore, the art of identifying such agents is unpredictable for the reasons stated above.
Likewise, as to making any fragment of a MASP-2 antibody to inhibit MASP-2-dependent complement activation the skilled artisan would be quite unsure about their ability to inhibit the lectin pathway of complement with, e.g., an Fc antibody fragment. While the skilled artisan might imagine the classical pathway of complement activation could be influenced by administering antibody Fc fragments far more than routine experimentation would be required to determine how such as fragment can also inhibit MASP-2-dependent complement activation.
In sum, making the genus of MASP-2 inhibitors encompassed by the instant claims is a highly unpredictable endeavor requiring far more than a skilled artisan’s knowledge of the art and routine experimentation. Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Conclusion
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of inhibitory agents.
Sufficient description to show possession of such a genus “may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus.” See University of California v. Eli Lilly & Co., 119 F.3d 1559, 1567, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997). Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 69 USPQ2d 1886 (Fed. Cir. 2004).
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Moreover, according to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, especially page 1106 3rd column, 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. 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.
What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, MPEP 2163 II.A.3a.ii.
No claims are allowed.
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/ZACHARY S SKELDING/Primary Examiner, Art Unit 1644
1 This interpretation of claim 1 is considered to be obtuse because it conflicts with how the skilled artisan would understand the meaning of claim 1 given the teachings of the instant specification and the plain meaning of the words of claim 1.
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