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 7/26/23. Claims 1, 3-11, and 14-23 are pending and under examination.
Notice
Applicant is advised that should claim 3 be found allowable, claim 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
As noted below, “optional” claim language is not being interpreted as limiting the claim in any way. As such, claim 3 written in independent form is identical to claim 7 but for the preamble in claim 7 of “treating a subject”. However, both subjects have the same disease and are administered the same therapeutic antibody. “Treatment” in the claim is being used as “administered”, e.g., “treating a subject with an anti-C1s antibody” is not defining the treatment of any particular disease or symptom but rather the patient themselves and any administration of the antibody to the patient is “treating a subject” with the antibody. Moreover, there are no active steps or limitations which would distinguish one method from the other and so claim 3 is inherently treating the disease as the same drug administered to the same person with the same disease must achieve the same results. MPEP § 2112 (II) states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC SCalif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products.
Applicant is advised that should claim 4 be found allowable, claim 5 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 4 written in independent form is identical to claim 5 but for the preamble in claim 5 of “treating a subject”. However, the only defining feature of the subject in both claims is that they have fatigue. Both subjects are administered the same therapeutic antibody. “Treatment” in the claim is being used as “administered”, e.g., “treating a subject with an anti-C1s antibody” is not defining the treatment of any particular disease or symptom but rather the patient themselves and any administration of the antibody to the patient is “treating a subject” with the antibody. Moreover, there are no active steps or limitations which would distinguish one method from the other and so claim 4 is inherently treating the disease as the same drug administered to the same person with the same condition must achieve the same results. MPEP § 2112 (II) states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC SCalif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products.
Applicant is advised that should claim 6 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Both claims 6 and 8 require:
1) the subject has a complement mediated disease (claim 8 depends from claim 7 which has this requirement),
2) the subject has fatigue (claim 6 depends from claim 5, which has this requirement)
3) the subject is treated with an anti-C1s antibody and IL6 or IL10 is measured (claim 8 depends from claim 7 with this requirement while claim 6 depends from claim 5 with this requirement).
While the dependency of the limitations “has fatigue” and “has a complement mediated disease” is reversed, claims 6 and 8 written independently arrive at an identical claim scope.
Claim Interpretation
Claim 14 recites “monitoring…over a period of time”. The specification at p.9 provides examples such as “1 week”. Thus, while assessing the level once as required in claim 1 takes some amount of time, a reasonable interpretation of “monitoring” requires at least two data points, though these two points may be separated by any amount of time.
Claim Objections
Claim 10 is objected to because of the following informalities:
Option b states “if the level of IL-6, and/or IL-10 in the sample is within 10% of baseline and/or fatigue the subject is maintained or worsens relative to baseline”. It appears that a word in the claim has been inadvertently omitted, e.g., “fatigue [in] the subject”, similar to option a.
Appropriate correction is required.
Claim 17 is objected to because of the following informalities: the claim recites H-CDR2 comprises “SEQ ID NO: 5 6”. There is no SEQ ID NO: 56 supplied in the sequence listing and so this appears to be a typographical error, meant to read “5 or 6”. 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.
Claims 3 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 3 recites the broad recitation “wherein the subject has a complement-mediated disease”, and the claim also recites “a classical complement-mediated disease” and “CAD” which is the narrower statement of the range/limitation, i.e., the latter two are species of the first claimed genus. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required (not the metes and bounds of the patent protection desired), or (b) a required feature of the claims. It is noted that the claim uses the term “optionally”, which may or may not be indefinite (MPEP §2173.05(h)(II)). However, in this case, it is not clear that these are claim limitations. In one case, the use of “optionally” is used to define a series of increasingly narrow conditions. However, if this is the case, the claim is limited to “the subject has CAD” and the previous recitations do not appear to add limitations but only potentially confuse the claim. In another case, these are merely preferences—the condition could be CAD but does not need to be—in which case such preferences do not belong in the claim. 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." As noted above, a claim defines the metes and bounds of the patent protection desired; if these options are not limiting the claim, they do not define the metes and bounds of the patent protection desired.
The same is true of claim 10. The claim specifies the levels might be reduced “optionally by at least 10%”. This appears to be a preference, which does not belong in the claims as it does not serve to limit the claim scope. Alternately, this is a limitation and a broad limitation followed by a narrow limitation is indefinite as above.
Therefore, claims 3 and 10 are indefinite.
Claim 10 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 10 provides two conditionals: if the level in the sample is reduced or if the level of the sample is within 10% of baseline. First, this baseline level is never measured according to the claims and so it is unclear how the method is meant to operate—how one is meant to make this decision—when the practitioner does not know what the levels are. Clarity would be improved by positively stating that these levels are measured. Second, there exists an overlap where it is unclear what should happen. If the levels are, e.g., 5% below baseline, then the levels are both “reduced” (option a) and “within 10% of baseline (option b); however, the actions taken in the two options are mutually exclusive: either the current treatment is continued or the current treatment is altered. It is unclear if one option has priority over the other or, if the levels meet the criteria of both, then the claim is infringed regardless of what action or inaction is taken.
Therefore, claim 10 is indefinite.
Claim 16 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 16 sets forth limitations regarding how the fatigue is assessed. However, this claim depends from claim 1, where assessing fatigue is optional. Thus, it is unclear if claim 16 is requiring that fatigue is actually assessed or if claim 16 is directed solely to this “optional” limitation. In other words, it is unclear if claim 16 would be infringed even when fatigue is not assessed because it is only an optional (preferred) embodiment of claim 1.
Therefore, claim 16 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.
Claim 9 is 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.
The limitations of claim 9 are that the subject has a baseline level of IL6 or IL10 prior to treatment or the subject has a baseline level of fatigue; this level does not need to be measured according to the claim, only that the subject “has” it. Neither of these, however, further limit claim 1. There is no particular value in the claim and so any level at all—including zero—is a “baseline” level by definition. There is no possibility that the subject fails to have a baseline level and so claim 9 fails to further limit claim 1.
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 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.
Claim 16 is 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 assessing fatigue, does not reasonably provide enablement for using the single claimed assessment to compare two different values (the “optional” step). 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.
Claim 16 recites an optional step. While this is not interpreted as a claim limitation, it nevertheless must be enabled when that option is exercised. In this case, there is only one claimed measurement, yet this single datapoint is used to assess “improvement…relative to baseline” when there is no baseline assessed and only one measurement is required. Either this assessment is prior to therapy, in which case it represents the baseline and no improvement is evaluated, or it occurs after the therapy, in which case the baseline was never measured. This method is also performed according to claim 1, where the subject need not even have fatigue (it is “optional”).
Therefore, claim 16 is not enabled for the full scope.
Claim 3 and 6 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 3 and 6 recite the genus of “classical complement-mediated disease”. A compliment mediated disease is one which C1s is higher or lower than a “normal” amount, e.g., p.40. However, the specification does not define any core characteristic to distinguish the sub genus of “classical” complement mediated diseases.
For a representative number of species, where a genus is claimed, the specification must disclose sufficient information to reflect the variation in the genus. The specification provides immunothrombocytopenic purpura (p.41 L18-19). While the specification discloses other complement-mediated diseases, it does not clearly indicate which of those diseases are “classical”. Thus, the specification discloses only a single member of the genus of “classical” complement-mediated diseases, which is insufficient to convey to the skilled artisan that Applicant was in possession of all such diseases as there is no indication of any shared characteristic nor any way to determine the variability in the genus from a single point.
Therefore, claims 3 and 6 do not meet the written description requirement.
Claim 17 is 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 17 recites that H-CDR2 comprises SEQ ID NO: 5 or 6 (see claim objection above). However, the specification as filed does not exemplify any antibody comprising SEQ ID NO: 5 in the H-CDR2 position. Table 1 only discloses this position as being SEQ ID NO: 6.
It is well-known in the art that specificity of an antibody stems from the interaction of six CDRs and CDRs are not generally recognized as interchangeable. Rather, the art recognizes that even slight changes to an antibody may unpredictably alter the binding properties of that antibody. See for example Kussie (IDS 7/26/23, NPL, no citation number provided) 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). Thus, there is no expectation that duplicating a CDR—replacing CDR2 of SEQ ID 6 with the CDR1 of SEQ ID 5—would provide the same required binding properties as claimed.
Therefore, claim 17 does not meet the written description requirement.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 10 and 11 are rejected under 35 U.S.C. 101 because:
Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A prong 1. The claims are a method and fall within the statutory category of a process.
Step 2A, prong 1: Prong 1 requires the Examiner to evaluate whether the claim recites a judicial exception and, if so, proceed to prong 2. In this case, the claims recite “if the level” of certain biomarkers is reduced or the same, certain actions are taken. Thus, the claims recite the correlation between biomarkers (IL6, IL10, or fatigue) and a treatment decision.
Step 2A, prong 2: Prong 2 requires the Examiner to evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception and, if not, proceed to step 2B. In order to integrate the recited judicial exception into a practical application, the claim will apply, rely on, or use the judicial exception that imposes a meaningful limit such that the claim is more than a drafting effort to monopolize the judicial exception. Examiners evaluate integration by identifying additional elements in the claim beyond the judicial exception and evaluating those elements individually and in combination to determine whether they integrate the exception in to a practical application. Examples that have been found by the Courts in which the exception was not integrated into a practical application include:
Mere instructions to implement an abstract idea on a computer
Adding generic instructions that the judicial exception should be used ("apply it")
Adding insignificant extrasolution activity to the exception ("mere data gathering")
Generally linking the use of the exception to a particular technological environment or field of use
In this case, the measurement of IL6 and IL10 are part of the data gathering step and so represent “mere data gathering”. Further, these values may not even be used in the decision, as the claims do not require any assessment of fatigue but the claims alternately use the correlation between fatigue and the treatment decision, disregarding the IL6/IL10 levels.
The actual administration of a therapeutic may reach the level of a practical application. However, as per the October 2019 examples, mere treatment is not necessarily enough. Specifically, when the claim covers where the treatment is “recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome into account”, the limitation is “at best nominal”. Essentially, if the treatment amounts to “apply it”, then this is not a practical application. Here, where there is a reduction of >0% and within 10%, the calculation has no bearing on the decision which covers changing the treatment in any way or not changing the treatment at all. Part b further amounts to simply “apply it” as the antibody treatment may be changed in any possible way, including increasing dosage, decreasing dosage, increasing/decreasing frequency, or even adding other, unrelated treatments, e.g., “further treatment of the subject to improve fatigue” when the subject is not claimed as having fatigue or including an anti-inflammatory when there is no limitation that the subject has an inflammatory disease (claim 11). Overall, while the judicial exception is claimed that certain measurements are correlated to treatment decisions, there is no apparent application of that correlation when making the decisions, said decisions being recited at a high level of generality such that it covers every possible treatment decision. Further, claim 1 is not a method of treatment in the sense of treating a disease as the subject of claim 1 is not claimed as having any disease nor are they being treated for a disease. The administration of a C1s antibody is for any reason with no particular outcome required. “Treatment” in the claim is being used as “administered”; see e.g., claim 9 which specifies “treatment with the anti-C1s antibody”. The subject’s “baseline level of fatigue” could be a normal, expected baseline or even zero (no fatigue) while the baseline level of IL-6 and IL-10 may also be normal and not in need of adjustment. There is no claimed purpose of administering the C1s antibody and so instructions to maintain or alter that treatment are also devoid of any practical application.
Step 2B: Where a claim does not integrate the exception, a claim may nevertheless be patent eligible, for example where additional elements are “significantly more” than the exception such that the additional elements were unconventional in combination. Considerations include whether or not the claim adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; or simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
In this case, the claims measure IL-6 and IL-10 by any possible means, which is recognized by the Courts to be well-understood and routine (MPEP 2106; Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)). Administering an anti-C1s antibody was also routine and conventional. See:
Roth (first Roth citation on IDS 7/26/23, NPL, no citation number provided)
Roth (second Roth citation on IDS 7/26/23, NPL, no citation number provided)
Van Vlasselaer (US 9074004; IDS 7/26/23, US Patent documents, no citation number provided)
Rosenthal (US20160326237; IDS 7/26/23, US Patent documents, no citation number provided)
Rosi (US 20200140533; effective filing date 11/2/18; form 892)
As these two steps (administering C1s antibody and measuring IL6/IL10) were routine and conventional, they do not make the claim patent eligible. While the combination of steps may make a claim eligible, this is not the case where those steps “simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception”. The relationship between the administration and the measurement is not claimed nor required. Since there is no claimed relationship between the two steps, they are fairly considered separate, unrelated steps.
Therefore, claims 10 and 11 are not patent eligible. It is noted, however, that measuring IL6 and IL10 to make treatment decisions about C1s antibody treatment as a combination was unconventional and would make the claims patent eligible. However, as claimed, the decision may be made on fatigue alone without any requirement that the IL6 or IL10 information is used in any way and currently the two populations overlap, meaning that the claim covers embodiments where the information does not actually inform the decision as it indicates either course of action is acceptable. That embodiment—where the measurement of IL6 and IL10 is entirely separate from the judicial exception—is not patent eligible which makes the claim as a whole patent ineligible. Further note that whether or not the combination was routine or conventional does not control whether or not such a combination would have been obvious, as they are different legal standards.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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 as of the effective filing date of the claimed invention(s) 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 as of the effective filing date of the later invention 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(s) 1, 3-11, 14-19, and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vlasselaer (WO2018170145; IDS 7/26/23, no citation number provided) in view of Ulvestad (form 892).
Regarding claim 1, Vlasselaer teaches inhibiting complement activation in an individual (subject) (abstract) by administering an anti-C1s antibody (abstract). Vlasselaer teaches this administration to treat cold agglutinin disease (CAD; figure 1; paragraph 346).
Vlasselaer does not teach measuring IL-6 levels.
Ulvestad teaches that, in patients with CAD, an increase in IL-6 leads to hemolysis (abstract). Ulvestad states “haemolysis in CAD is controlled by the availability of early classical pathway complement molecules and that hemolysis following acute phase response occurs as a consequence of increased complement synthesis” (abstract). Ulvestad also teaches that IL-6—a proinflammatory cytokine—“plays a major role in fever induction” and that the acute production of proinflammatory cytokines leads to the complement-mediated hemolysis (p.241 C2).
It would have been obvious to one of ordinary skill in the art at the time of filing to both measure IL-6 in a sample of a subject and administer an anti-C1s antibody to the subject, arriving at the instant claim. Ulvestad teaches that increased IL-6 is indicative of pathology (hemolysis) in CAD and teaches methods of measuring this biomarker. Vlasselaer teaches anti-C1s is a known therapy for CAD and one which inhibits complement activation, which would be further desirable given that Ulvestad teaches increased complement synthesis leads to hemolysis. The combination of these two—administering a therapeutic and measuring a biomarker—would have led to the predictable outcome of the disease being treated and the IL-6 levels being measured; see KSR rationale A. The only difference between the instant claim and the prior art is the actual combination of the two steps, yet their combination does no more than perform the same function as each step does separately and the results would have been predictable.
Regarding claim 3, CAD is a complement mediated disease.
Regarding claim 4, Vlasselaer teaches the treatment of CAgD (cold agglutinin disease) with the anti-C1s antibody acts to “improve fatigue” (paragraph 345). In evaluating the efficacy of the antibody, one of the secondary endpoints was evaluating the mean change in fatigue using the FACIT-F scale (paragraph 479). One of the inclusion criteria was presence of fatigue as a CAgD (CAD)-related symptom (paragraph 481). Thus, Vlasselaer teaches fatigue is a symptom of the disease to be treated (CAD), was a desirable symptom for a subject to be experiencing prior to treatment with the anti-C1s antibody, and provides a reason to expect the C1s treatment will ameliorate the fatigue. This would have made it obvious to one of ordinary skill in the art at the time of filing to include a subject having fatigue.
Regarding claim 5, this is a duplicate of claim 5 (see above) and would have been obvious for the same reasons. To the extent that “treating a subject” differentiates the claims—which is not conceded by the Examiner—the teachings of Vlasselaer are that the antibody will treat the subject as noted above.
Regarding claim 6, the subject having fatigue (according to claim 5) would have been obvious as discussed above regarding claim 5. The subject having a complement mediated disease, such as CAD, would have been obvious as discussed above regarding claim 3. Further, Vlasselaer teaches explicitly that fatigue is a symptom of CAD as noted above. Thus, claim 6 would have been obvious for the same reasons.
Regarding claim 7, this is a duplicate claim of claim 3 and would have been obvious for the same reasons. To the extent that the preamble “treating a subject” differentiates the claims—which is not conceded by the Examiner—the teachings of Vlasselaer are that the antibody will treat the subject as noted above.
Regarding claim 8, this claim would have been obvious for the same reasons as claim 6 for the reasons discussed with regard to claim 6 as well as because claim 8 is a duplicate of claim 6.
Regarding claim 9, as noted in the §112d rejection above, any subject necessarily has a “baseline” level prior to the treatment. As Vlasselaer treats the subject, whatever level the subject had prior to that treatment is the baseline. The claim does not require measuring this baseline and so represents an inherent feature of the subject. Further, Ulvestad measures IL-6 in the subjects as described above. Since Ulvestad does not teach these subjects had been administered an anti-C1s antibody, this measurement meets the instant limitations of a baseline prior to such administration.
Regarding claim 10, as described above, Ulvestad teaches increased IL-6 is seen in subjects with CAD which leads to hemolysis. Further, the antibody of Vlasselaer is meant to inhibit the complement-mediated pathway. It would have been obvious to one of ordinary skill in the art that if a known biomarker of disease—IL-6—is improving (is reduced), then the therapeutic is having the intended treatment effect and should be continued. See MPEP 2141(II)(C): "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396.
Regarding claim 11, Vlasselaer teaches the treatment can reduce fatigue associated with CAD as discussed above. Thus, where a specific dosing regimen of the anti-C1s antibody results in “fatigue [in] the subject is maintained or worsens relative to baseline”, it would have been within the ordinary skill and inferences of the ordinary artisan to adjust the dosing or frequency, such as by increasing the therapeutic amount, or by including “further treatment of the subject to improve fatigue”. This latter category is not limited to any particular treatment and so it would have been within the ordinary skill in the art to include an additional therapeutic to improve fatigue upon observing that fatigue was not improving as desired. Moreover, Vlasselaer teaches adding additional pharmaceutically active compounds (paragraph 269). Vlasselaer also teaches various dosages and frequencies (starting at paragraph 286). Thus, Vlasselaer recognizes dosing as a result-effective variable and, if therapeutic outcomes such as fatigue improvement are not being realized, the person of ordinary skill in the art would have found it obvious to adjust these variables to optimize the outcome. See MPEP 2141(II)(C): "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. See also: “it is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions” (MPEP §2144.05(II)(A)).
Regarding claim 14, Ulvestad measures IL-6 over a period of time (table 1), making such a step obvious. Moreover, given the role of IL-6 described by the art in the disease pathway, a person of ordinary skill in the art would have recognized that these levels are indicative of the disease state and could be monitored during therapy (Id. at 418, 82 USPQ2d at 1396).
Regarding claim 15, the subject in Ulvestad received a blood transfusion for the hemolysis (p.240 C1). Thus, blood transfusions were a known treatment for hemolysis in a subject with CAD. It would have been obvious to one of ordinary skill in the art that receiving a blood transfusion previously would not be expected to alter the efficacy of the anti-C1s antibody and so one would have found it obvious to perform the method as described above on a subject with CAD even when they had previously undergone a blood transfusion. Moreover, Vlasselaer teaches administration of the antibody to subjects “who have a recent history of blood transfusion” (example 6).
Regarding claim 16, Vlasselaer teaches assessing fatigue according to the FACIT-F score (paragraph 479).
Regarding claims 17-19, Vlasselaer teaches the antibody has the heavy chain sequence of SEQ ID NO: 22, which is identical to instant SEQ ID NO: 1 (claim 19). Vlasselaer also teaches the antibody has a light chain sequence of SEQ ID NO: 23, which is identical to instant SEQ ID NO: 2 (claim 19). As instant claim 19 depends from claim 18 which depends from claim 17, the sequences in claims 17 and 18 are also in the Vlasselaer antibody.
Regarding claim 23, Vlasselaer teaches the exemplary antibody BIVV009, which has the above sequences, is the IgG4 isotype (paragraph 387).
Therefore, claims 1, 3-11, 14-19, and 23 would have been obvious.
Claim(s) 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vlasselaer/Ulvestad as applied to claims 1, 3-11, 14-19, and 23 above, and further in view of Panicker (WO2018071676; IDS 7/26/23, no citation number provided).
The teachings of Vlasselaer and Ulvestad are discussed above and incorporated herein. Neither teaches the antibody of instant claims 20-22.
Like Vlasselaer, Panicker is also concerned with administering an anti-C1s antibody to inhibit the complement pathway and treat cold agglutinin disease (abstract; paragraph 243). Panicker teaches the anti-C1s antibody comprising SEQ ID NO: 29, which is identical to instant SEQ ID NO: 11 (claim 22). Panicker also teaches the antibody has a light chain sequence of SEQ ID NO: 30, which is identical to instant SEQ ID NO: 12 (claim 22). As instant claim 22 depends from claim 21 which depends from claim 20, the sequences in claims 20 and 21 are also in the Panicker antibody.
It would have been obvious to make a simple substitution for one known anti-C1s antibody which treats CAD (Vlasselaer) with another (Panicker) because the antibodies were both known in the art, both known to possess the same therapeutic function, both known to bind the same target, and one could have made the substitution with an expectation of achieving the same predictable result.
Therefore, claims 20-22 would have been obvious.
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 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); 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10450382 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
The reference claims are directed to an anti-C1s antibody with the same CDRs as instant claim 17 and within the scope of instant claim 1. Where a reference document is directed to a composition of matter, the specification may be inspected for the uses of that composition when making a double patenting determination. See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office’s use of disclosed utilities of compositions when applying double patenting rejections to method claims.
In this case, C13 describes the antibodies inhibition of CAD-associated hemolysis in subjects with CAD and describes administering the antibody to treat CAD (C86). This disclosed utility therefore represents an obvious variation/anticipates the instant methods of instant claims 1, 3, 6, 7, 9, 17, and 23 with respect to administering (“treating the subject with”) the anti-C1s antibody. The teachings of Ulvestad are discussed above and incorporated herein, which address the obviousness of including the claimed IL-6 assessment. The remaining instant claims represent an obvious variation of the claimed composition and disclosed utilities in the reference document as set forth in the §103 rejection above regarding the teachings of Vlasselaer, Ulvestad, and Panicker, which are incorporated herein. To sum, the reference invention is an anti-C1s antibody which treats CAD, which is also the invention of instant claim 1. The remaining limitations represent obvious variations of the reference claims.
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 8877197 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
The reference claims are directed to an anti-C1s antibody with the same CDRs as instant claim 17 and within the scope of instant claim 1. Where a reference document is directed to a composition of matter, the specification may be inspected for the uses of that composition when making a double patenting determination. See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office’s use of disclosed utilities of compositions when applying double patenting rejections to method claims.
In this case, C13 describes the antibodies inhibition of CAD-associated hemolysis in subjects with CAD and describes administering the antibody to treat CAD (C86). This disclosed utility therefore represents an obvious variation/anticipates the instant methods of instant claims 1, 3, 6, 7, 9, 17, and 23 with respect to administering (“treating the subject with”) the anti-C1s antibody. The teachings of Ulvestad are discussed above and incorporated herein, which address the obviousness of including the claimed IL-6 assessment. The remaining instant claims represent an obvious variation of the claimed composition and disclosed utilities in the reference document as set forth in the §103 rejection above regarding the teachings of Vlasselaer, Ulvestad, and Panicker, which are incorporated herein. To sum, the reference invention is an anti-C1s antibody which treats CAD, which is also the invention of instant claim 1. The remaining limitations represent obvious variations of the reference claims.
It is noted that Applicant has filed numerous patent applications covering the C1s antibodies and their use in treating complement mediated diseases including specifically CAD. The Examiner has endeavored to discover such documents. However, it is noted for the record that where Applicant or a shared inventor is listed on a pending US application or US Patent that claims an anti-C1s antibody, such document would serve as the basis for a non-statutory double patenting rejection for essentially the same reasons as listed above. The following documents were discovered and the rejection headers provided; however, the body of the rejection is not reiterated as it is essentially duplicative of the two recited above and should be considered incorporated therein, as either the reference documents claim an anti-C1s antibody as a composition and disclose the utility of treating CAD or else claim a method of administering an anti-C1s antibody to a subject. The inclusion of the IL-6 or IL-10 assessment represents an obvious variation as discussed, particularly with respect to Ulvestad, and the symptoms of the disease (e.g., assessing fatigue) or the particular C1s antibody would have been obvious as discussed, particularly with respect to Vlasselaer and Panicker.
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-47 of U.S. Patent No. 8945562 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 9074003 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9074004 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9206259 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
Claims 1, 3-11, and 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9562092 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
Claims 1, 3-11, and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 35-36, 38-40, 42-43, 48, 57-58, 60-61, 69, 74-76, 80 of copending Application No. 19068758 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-11, and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 8-9, 11-12, 14-15, 17, 19, 21-25, 27-29, 31, 33, 36-40, 42, 45 of copending Application No. 18334567 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-11, and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18919489 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-11, and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-16, 18, 20, 22, 24, and 27 of copending Application No. 18477981 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-11, and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-16, 18, 20, 22, 24, and 27 of copending Application No. 18477981 in view of Vlasselaer (WO2018170145), Ulvestad, and Panicker (WO2018071676).
This is a provisional nonstatutory double patenting rejection.
Note that co-pending application 18340797 was considered. However, the currently pending claims of that application are all limited to treatment of CIDP. While this is a complement-mediated disease, Ulvestad does not render obvious the inclusion of measuring IL6 or IL10 when treating CIDP. Thus, no double patenting rejection over this application has been made at this time.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Choe (US 20190175663; form 892) teaches CAD is an IL-6 mediated disease (claims 1 and 5) and teaches assessing the level of IL-6 (claim 4).
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/Adam Weidner/ Primary Examiner, Art Unit 1675