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 (i.e., changing from AIA to pre-AIA ) 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
This action is in response to claim amendments filed 7/29/25. Claims 56-75 are pending and under examination.
Drawings
The drawings filed 7/29/25 contain at least one drawing in color with no corresponding petition to accept color drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, e.g., p.20. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 75 is objected to because of the following informalities: the claim lists “psoriasis” twice. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 65 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 65 lists three limitations A-C. However, there is no transition (“and” or “or”) before the last item. It is unclear if these are all required (A, B, and C) or alternatives (A, B, or C). There is nothing per se incompatible about the three options and so they might all be required. Alternately, this may be intended as a Markush group.
Therefore, claim 65 is indefinite. The broadest reasonable interpretation is that these are alternatives (“or”) and has been examined under this interpretation.
Claim 73 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 73 sets for what the method of claim 72 is “for”. Claim 72 is either a “method of treating an OX40 mediated disorder” or “a method of reducing or inhibiting T-cell proliferation”.
First, there is no special definition of “reducing” or “inhibiting” in the specification. Under an ordinary definition, it is unclear what difference, if any, these terms convey. If T-cell proliferation has been reduced, then it has been inhibited. Conversely, if proliferation was inhibited, it was reduced.
Second, the preamble of claim 72 is considered a limitation of the claim. If an OX40 mediated disorder is unaffected, then administering the antibody would not be “treating an OX40 mediated disorder”. If T-cell proliferation is not reduced/inhibited, then administration does not fall within the scope of “a method of…reducing or inhibiting T-cell proliferation”. This differs from claim 73. The phrase “for reducing…” is unclear. In one interpretation, this claim limitation is meant to indicate that the claims are directed to the second option of claim 72, i.e., the method is a method of reducing/inhibiting T-cell proliferation and not a method of treating an OX40 mediated disease. This is supported by reciting only one of the two options in claim 72. In another interpretation, this “intended use” does not impart any limitation on the claim but rather indicates the intention of the user rather than an actual result (MPEP §2111.02(II)). This is supported by using distinct claim language from that of claim 72. It is unclear what the scope of claim 73 is meant to cover.
Therefore, claim 73 is indefinite.
Claim 75 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 75 lists diseases to be treated. This list is indefinite. The claim uses language “such as”, “including”, and “as well as”. The term “including” is synonymous with “comprising” (MPEP §2111.03) but including open ended language in a list of alternatives is not compliant; see MPEP§2173.05(h) which states if a material is selected from an open list of alternatives the claim should generally be rejected under §112(b) because it is unclear what other alternatives this list “includes”. It is unclear if “as well as” is meant as comprising and, if so, would suffer the same deficiencies.
Further, using these terms, e.g., “such as”, makes it unclear if these are limitations or examples. The claim states “ischemic diseases such as myocardial infarction as well as atherosclerosis”. If these are limitations (ischemic disease is limited to myocardial infarction and atherosclerosis) then it is unclear why the terms “such as” and “as well as” are in the claim. If they are not intended as limitations, then it is unclear why the terms are in the claim at all. See MPEP § 2173.05(d) which states that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim."
It is also unclear how far down the list the “such as” is meant to cover. The first instance of “such as” is in line 7. One interpretation is that every member of the list from “multiple sclerosis” through the last item (vitiligo) is meant as an example of “disorders of the central and peripheral nervous system”. In another interpretation, only multiple sclerosis is offered as an example of this genus.
Finally, the claim uses parentheticals to define acronyms. However, the claim also recites “trauma (surgery)”. It is unclear if the claim is meant to cover all forms of trauma and offers surgery as an example or if the claim is limited to surgical trauma. The term “surgery” is not a known acronym or synonym for “trauma” and so it appears the parentheticals are used differently than the other uses, but what that use implies is unclear.
Therefore, claim 75 is indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 67-70 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.
Claim 67 is a nucleic acid encoding the heavy chain CDRs or the light chain CDRs of claim 60. Claim 60 is an antibody that requires both the heavy chain and light chain CDRs.
As such, claim 67 seeks to broaden the claim by not requiring both heavy and light chain CDRs, which violates the requirements of §112(d). Claims 68-70 depend from claim 67 and are deficient for the same reasons. Note that claim 70 produces an antibody or antibody fragment but recites the host cell expressing “a polypeptide or polypeptides”. An antibody is not a single polypeptide and so this claim is interpreted as including expressing only a heavy or light chain as per claim 67, from which claim 70 depends. Thus, claim 70 also has the deficiencies above.
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.
Claims 72-75 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for ameliorating at least one symptom of certain OX40 diseases and inhibiting certain OX40 diseases, does not reasonably provide enablement for preventing or causing regression of OX40 diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: 1) nature of the invention, 2) breadth of claims, 3) amount of direction or guidance by the inventor, 4) relative skill of those in the art, 5) level of predictability in the art, 6) state of the prior art, 7) existence of working examples, and 8) quantity of the experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The nature of the invention is affecting an OX40 disease, including fully preventing the disease, curing the disease, and ameliorating symptoms of the disease. The specification at paragraph 72 clearly includes this scope in the definition of the term “treatment”. It is noted that the specification states the term “treatment” refers to “treatment”, where using the same word in the definition of that word creates a circular interpretation; however, this paragraph is still clear as to the embodiments included within the scope.
The breadth of the claims includes preventing, curing, and ameliorating all OX40 diseases including those in claim 75; note that while claim 73 requires the subject “has an OX40 mediated disorder”, the use of “an” clearly indicates this need not be the disease “treated” by claim 72. These diseases span a broad range of diseases with differing symptoms, populations, and etiologies. While OX40 may have a role in these diseases, few of them are caused by OX40 alone.
For example, claim 75 lists Alzheimer’s disease. Alzheimer’s disease is not generally recognized as caused by OX40 or an OX40 mediated disease but rather amyloid beta and/or tau (Reitz). Moreover, the art currently does not recognize any drug or method that results in the complete prevention or cure/regression of Alzheimer’s disease. Reitz (cited on form 892) states “as the currently available drugs only slightly affect disease severity and progression, AD remains at present effectively untreatable” (p.2 C1) and Stanford (cited on form 892) that states "unfortunately, there are no currently available FDA-approved medications proven to delay or slow progression of the underlying brain degeneration and loss of synaptic connections that occurs in Alzheimer’s disease”. Where the goal is recognized as difficult and as-yet unrealized, the evidence supporting a claim that such a result is achievable must necessarily be strong. The instant specification does not provide any working examples of AD prevention nor does it provide adequate guidance on how to overcome the art-recognized difficult nature of this goal. While there is a reasonable expectation that symptoms associated with the role of OX40 in the disease may be affected, one skilled in the art could not practice the method of the claims to achieve the result of prevention of AD nor the regression of AD as claimed. This same rationale can be extended to other members of the list. There is no evidence that a “surgical adhesion” is caused by T-cell proliferation or OX40. There are many “disorders of the central and peripheral nervous system” not caused by OX40 or T-cell proliferation. While claim 75 defines this genus as within the scope of “OX40 mediated disorder”, there is no requirement that the phrase “disorders of the central and peripheral nervous system” means OX40 is related to the disease because Applicant is allowed to be their own lexicographer and may define all such disorders as OX40 mediated disorders irrespective of the actual role of OX40. If the role of OX40 is implicit in the claim, it would still be undue experimentation to determine which central/peripheral nervous disorders are associated with OX40 and whether or not reducing T-cell proliferation would prevent/cure those diseases. The claim also lists “trauma (surgery)”. There is no basis for expecting administration of this antibody would, e.g., prevent surgical trauma such as scalpel cuts.
The specification provides in vitro experiments demonstrating the effect on T-cells. There is also an example demonstrating safety in monkeys, though these monkeys are not disclosed as having any disease nor does the specification in general appear to reduce to practice the treatment of any disease in vivo in any subject. While in vitro results are given weight when they correlate to a disease (MPEP §2164.02(II)), there is no rationale for expecting the disclosed effect on T-cells would prevent or reverse Alzheimer’s disease given the known intractable nature of the disease and the fact that OX40/T-cells are not generally recognized as the primary etiological agent.
Taking the evidence as a whole, it would require undue experimentation to test every OX40 disease under the myriads of administration parameters to find those that might prevent or regress such diseases as there would be no reasonable expectation of success when attempting to, e.g., prevent a disease not caused by OX40 with an OX40 antibody, particularly those that heretofore are uncurable and unpreventable. The claim is replete with diseases that are unsupported with a reasonable expectation that the instant method would cure/prevent the disease.
The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
"[T]o be enabling, the specification.., must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" Wright, 999 F.2d at 1561, 27 USPQ2d at 1513 (emphasis added), quoted in Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997). Thus, "there must be sufficient disclosure, either through illustrative examples or terminology, to teach those of ordinary skill how to make and how to use the invention as broadly as it is claimed." In re Vaeck, 947 F.2d 488, 496 & n. 23, 20 USPQ2d 1438, 1445 & n. 23 (Fed. Cir. 1991), quoted in Enzo Biochem, Inc. v. Calgene, lnc., 188 F.3d 1362, 1372, 52 USPQ2d 1129, 1138 (Fed. Cir. 1999).
"Patent protection is granted in return for an enabling disclosure..., not for vague intimations of general ideas that may or may not be workable." Genentech, 108 F.3d at 1365, 42 USPQ2d at 1005. "Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public [skilled in the art] to understand and carry out the invention." Id. at 1366, 42 USPQ2d at 1005 (emphasis added).
Therefore, claims 72-75 are not enabled for their full scope.
Allowable Subject Matter
Claims 56-64, 66, and 71 are allowed. Claim 56 is the sole independent claim. All other claims ultimately depend from claim 56 and so must have the same limitations. Claim 56 is an antibody or fragment thereof, which is defined by six CDRs.
It is well established in the art that the binding properties of an antibody are primarily defined by these six CDRs. Moreover, these CDRs are unpredictable. Disclosure of an antigen does not describe the antibody which binds that antigen. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor' s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11). Further, even single amino acid changes to a known CDR may have unpredictable effects on the binding of the antibody; see for example Kussie (cited on form 892) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., abstract).
The instant claims require either SEQ ID NO: 38 (qqxxxpwt) or SEQ ID NO: 71 (cqqxxxxpwt) where X is defined in the claim. Genbank (form 892) discloses a protein comprising SEQ ID NO: 38; however, Genbank is not an antibody nor does it disclose the combination of all six claimed sequences. There is no prior art that discloses a sequence meeting the limitations of SEQ ID NO:71. A rejection under §103 generally requires an element is either known or at least predictable. In this case, the combination of sequences was not known in the prior art and without explicit motivation to arrive at these sequences, such sequences were non-obvious.
Claim 72 is directed to “an OX40 mediated disorder”. This is not an established class of disease and there is no common property of such diseases beyond the definition of the genus (OX40 has some undefined role in the disease). However, claim 75 sets forth a representative number of species illustrative of the variation in the genus. As such, the phrase meets the written description requirement.
Claim 62 sets forth limitations for how the CDRs are defined. Claim 62 must still comprise the sequences set forth by claims 56 and 60 (§112(d)); however, these CDRs may comprise additional amino acids which would be dictated by how the CDRs are defined, e.g., by the systems in claim 62. Thus, claim 62 is deemed to meet the requirements of §112(d).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/ Primary Examiner, Art Unit 1675