Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species: 150 mg to 250 mg every 1-2 months, subcutaneous administration of the anti-FXII antibody at a dosage of between 70 mg and 700 mg, and a human patient having HAE in the reply filed 05/21/2025 is acknowledged.
Claims 19-26, 30-31, 35, 39-44, and new claims 46-48 are now under consideration in the instant Office Action.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 19-26, 30-31, 35, 39-44, and new claims 46-48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Panousis et al. (WO 2017/173494 A1, in IDS filed 06/02/2022).
Panousis et al. teaches an inhibitor of factor XII (FXII), wherein the inhibitor is an antibody used in a treatment for atherosclerosis or “diseases related to FXII/FXIIa-induced kinin formation are selected from the group hereditary angioedema”, see page 17, lines 4-5. Panousis et al. teaches antibody sequences that read on the instantly claimed anti-FXII antibody, which comprise SEQ ID NOs: 1-6 as the heavy and light chain CDR sequences, SEQ ID NOs: 7-8 as the heavy and light chain variable region sequences, and SEQ ID NOs: 9-10 as the heavy chain and light chain sequence. Panousis et al. teaches sequences that anticipate the following instantly claimed sequences:
Instant SEQ ID NOs: 1-3 is a 100% match to Panousis’ SEQ ID NO: 20
Instant SEQ ID NOs: 4-6 is a 100% match to Panousis’ SEQ ID NOs: 7, 19, or 21
Instant SEQ ID NO: 7 is a 100% match to Panousis’ SEQ ID NO: 18
Instant SEQ ID NO: 8 is a 100% match to Panousis’ SEQ ID NO: 19
Instant SEQ ID NO: 9 is a 100% match to Panousis’ SEQ ID NO: 20, which includes a lysine linked to the last amino acid of the sequence
Instant SEQ ID NO: 10 is a 100% match to Panousis’ SEQ ID NO: 21.
Panousis et al. teach that the antibody containing the aforementioned sequences “can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass”, see pg. 24, lines 33-35. Panousis et al. also teaches how “in one example, a stabilized lgG4 constant region comprises a proline at position 241 of the hinge region according to the system of Kabat … this position corresponds to position 228 of the hinge region 10 according to the EU numbering… In human lgG4, this residue is generally a serine. Following substitution of the serine for proline, the lgG4 hinge region comprises a sequence CPPC. In this regard, the skilled person will be aware that the "hinge region" is a proline-rich portion of an antibody heavy chain constant region that links the Fc and Fab regions that confers mobility on the two Fab arms of an antibody. The hinge region includes cysteine residues which are involved in inter-heavy chain disulfide bonds”, see page 45, lines 5-18.
Panousis et al. teaches a dosage for treatment, ranging from “about 0.1 mg/kg to about 300 mg/kg, e.g., … for example about 10 mg/kg in one or more dose administrations daily, for one or several days” and that “the FXII inhibitor is administered at an initial (or loading) dose which is higher than subsequent (maintenance doses). For example, the FXII inhibitor is administered at an initial dose of between about 10 mg/kg to about 30 mg/kg. The FXII inhibitor is then administered at a maintenance dose of between about 0.0001 mg/kg to about 10 mg/kg”, see page 11 and page 55, lines 32-37. Therefore, when an exemplary subject weighs 80kg, the administered dosage when calculated using the rate of between about 0.0001 mg/kg to about 10 mg/kg would be 0.008mg-800mg. This value is encompassed by the instantly claimed range of 75-250 mg of instant claims 19 and new claims 46-48. Panousis et al. also teaches that “the maintenance doses may be administered every 7-100 days, such as, every 14 or 28 or 56 or 84 days”, see page 55, lines 28-37. Panousis et al. also teaches that the “the inhibitor of FXII is administered subcutaneously”, see page 9, lines 17-18. Panousis et al. teaches that the dosage for treatment can be used against “diseases related to FXII/FXIIa induced kinin formation are selected from the group hereditary angioedema, bacterial infections of the lung, trypanosoma infections, hypotensive shock, pancreatitis, chagas disease, articular gout, arthritis, disseminated intravascular coagulation (DIC) and sepsis”, see page 17, lines 4-7.
This meets the limitations of instant claims 19, 45, and new claims 46-48 wherein the CDR sequences, which are encompassed within the heavy and light chain variable regions as well as the heavy and light chain regions are taught by Panousis in a method of treating hereditary angioedema wherein the dosage is administered at a dosage of 75 mg to 250 mg when adjusted for body mass from within the taught ranges. This meets the limitations of instant claim 20 wherein the heavy and light chain variable region sequences are taught, instant claims 21 and 22 wherein the antibody is an IgG but more specifically an IgG4, instant claim 23 wherein a mutation to proline occurs at position 228 of the hinge region, instant claims 24 and 25 wherein SEQ ID NOs: 9-10 are taught complete with the additional lysine linked to the last amino acid, instant claim 30 wherein the dosage can be administered every 1-2 months, instant claim 31 wherein the patient has a disease implicated by factor XII or HAE, and instant claim 35 wherein the inhibitor is administered subcutaneously to the subject.
While Panousis et al. does not explicitly teach that the dosage of antibody administered maintains a concentration of at least 5 μg/mL in a subject, it is clear that the taught dosages would have the same characteristics and would respond to the same treatment as the instantly claimed methods since there is no evidence to the contrary. Note that rejections for anticipation are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). 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)." In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same or an obvious variant; see MPEP § 2112(V). 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.
While the references are silent on the intended results in the instant claims 26 and 39-44, such as maintaining a specific concentration in the body or achieving a certain percentage reductions in the risk of a hereditary angioedema attack, the reference teaches the required antibody and dosage amounts. Therefore, the antibodies when administered will produce the same results as the instantly claimed method since one is practicing the active steps, administering the same antibody to the same patient population. MPEP 2145(II) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)” (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”).
Therefore, claims 19-26, 30-31, 35, 39-44, and new claims 46-48 are anticipated by Panousis et al.
Response to Arguments
Applicant's arguments filed 08/03/2026 have been fully considered but they are not persuasive.
Applicant argues “there are no examples in Panousis et al. where a human patient was treating for HAE with any FXII inhibitor”. This is not found persuasive.
Panousis et al. discloses treatments for atherosclerosis as well as “diseases related to FXII/FXIIa induced kinin formation are selected from the group hereditary angioedema, bacterial infections of the lung, trypanosoma infections, hypotensive shock, pancreatitis, chagas disease, articular gout, arthritis, disseminated intravascular coagulation (DIC) and sepsis”, see page 17, lines 4-7. As such, Panousis et al. does explicitly teach the treatment of hereditary angioedema within the reference. The treatment for the listed diseases entails the same exact antibody comprising SEQ ID NOs: 1-10 as instantly claimed (see above). Given that the structure is entirely identical and Panousis acknowledges the shared pathway implicated in the disease state, the antibody taught in the art would still bind to the antigen it was designated for regardless of what inventors manage to explicitly recite. Panousis may not explicitly recite every single disease that the antibody would treat via binding; however, the structure of the antibody of the prior art anticipates the instantly claimed antibody and as such would perform the same function as claimed and treat a disease such as hereditary angioedema, in addition to its explicit recitation of hereditary angioedema. It is unclear how Applicant claims that identical antibodies would not share the same functionality given that structure confers functionality of proteins.
Additionally, Panousis “studied the effects of FXII inhibition based on their understanding that this protein has effects on numerous biological pathways, some of which may be involved in atherosclerosis, e.g., inflammation”, see Summary. It is well known in the art that factor XII is implicated across a vast variety of diseases states, which all share the characteristic of triggering inflammation. As noted on page 17 of Panousis, the antibody of the prior art impacts kinin formation, which is a key initiator of the bradykinin-producing kallikrein-kinin pathway which is known to cause swelling in vascular and permeability related diseases. This is further bolstered by the evidentiary reference of Craig et al. (in PTO-892 filed 11/28/2025), which discloses that “hereditary angioedema is associated with dysregulation of the kallikrein–kinin system. Factor XII (FXII) is a key initiator of the kallikrein–kinin system, which produces bradykinin, a central mediator of angioedema across diseases”, see Summary. The state of the prior art recognizes that inhibiting factor XII would prevent its downstream effects, such as triggering inflammation, and serve as a potential therapeutic for diseases that affect inflammation. The pathway disclosed by Craig et al. is also the same pathway that Applicant argues on page 6 of their Remarks is implicated in the hereditary angioedema of the instant claims.
Given that the antibody of the prior art implicates the pathway isolated in hereditary angioedema and is the same pathway acknowledged by Applicant to be of focus in the instantly claimed method, Panousis continues to anticipate the instant claims as it functionally lays out how the antibody works on the pathways and how it can be applied to treat diseases with a shared etiology to atherosclerosis, like hereditary angioedema. While the prior art is titled for atherosclerosis, the teachings of the disclosure are far more extensive than just the one disease it is titled for. Applicant is reminded that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Applicant argues that “Panousis does not describe the subject matter of the presently pending claims as arranged in the claims”. This is not found persuasive.
As disclosed above, Panousis et al. anticipates all the elements of the instant claims as laid out. Applicant has only argued that the “missing element” Panousis et al. fails to teach is the species of hereditary angioedema, which was addressed in the arguments above. Panousis et al. teaches the same antibody, a broader range of dosages which encompasses the narrower range of the instant claims, and disease state as the instant claims, and cites a similar justification for using the invention as a treatment for hereditary angioedema by acknowledging the shared pathway of diseases that implicate the factor XII pathway.
In regards to the range of dosages, the Office arrives at the claimed dosage from a range taught in Panousis et al., wherein Panousis et al. teaches a dosage for treatment, ranging from “about 0.1 mg/kg to about 300 mg/kg, e.g., … for example about 10 mg/kg in one or more dose administrations daily, for one or several days” and that “the FXII inhibitor is administered at an initial (or loading) dose which is higher than subsequent (maintenance doses). For example, the FXII inhibitor is administered at an initial dose of between about 10 mg/kg to about 30 mg/kg. The FXII inhibitor is then administered at a maintenance dose of between about 0.0001 mg/kg to about 10 mg/kg”, see page 11 and page 55, lines 32-37. Therefore, when an exemplary subject weighs 80kg, the administered dosage when calculated using the rate of between about 0.0001 mg/kg to about 10 mg/kg would be 0.008mg-800mg. This value is encompassed by the instantly claimed range of 75-250 mg, which falls within the broader range taught by Panousis et al.
In the Remarks, Applicant discusses the wording of Panousis et al., stating that the intended effect of “wherein the human subject experiences a reduction in monthly HAE attack rate” is not listed verbatim and thus not a limitation contained within the prior art. However, Panousis et al. teaches hereditary angioedema as a disease on page 17, line 4. Since Panousis et al. teaches all of the limitations of the instant claims and barring evidence to the contrary, one of ordinary skill in the art would reasonably expect the same treatment to confer the same characteristics regardless of what limitations are described on paper.
Applicant argues that the “Office’s reliance on a broad range of 0.008 mg-800 mg of a general FXII inhibitor does not anticipate the presently claimed range of 75 mg to 250 mg of the recited antibody” and that the Office provided no rationale for how a skilled artisan could arrive at that range. This is not found persuasive.
As discussed in the anticipation rejection above, the Office arrives at the claimed dosage from a range taught in Panousis et al., wherein Panousis et al. teaches a dosage for treatment, ranging from “about 0.1 mg/kg to about 300 mg/kg, e.g., … for example about 10 mg/kg in one or more dose administrations daily, for one or several days” and that “the FXII inhibitor is administered at an initial (or loading) dose which is higher than subsequent (maintenance doses). For example, the FXII inhibitor is administered at an initial dose of between about 10 mg/kg to about 30 mg/kg. The FXII inhibitor is then administered at a maintenance dose of between about 0.0001 mg/kg to about 10 mg/kg”, see page 11 and page 55, lines 32-37. Therefore, when an exemplary subject weighs 80kg, the administered dosage when calculated using the rate of between about 0.0001 mg/kg to about 10 mg/kg would be 0.008mg-800mg. This value is encompassed by the instantly claimed range of 75-250 mg. However, that fact does not avoid a finding of prima facie obviousness in light of the overlap of the claimed range. “Selecting a narrow range from within a somewhat broader range disclosed in a prior art reference is no less obvious than identifying a range that simply overlaps a disclosed range.” In re Peterson, 315 F.3d at 1329—30.
Because a skilled person in the art would attempt to identify the optimal treatment dose amount and dosing schedule for an anti-FXII antibody when used a therapy and would increase the dose accordingly to reach the optimum dosing strategy, the method of instant claims is obvious over the teaching of Panousis et al. “(W)here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation” In re Aller, 220F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Additionally, there is sufficient teaching and guidance in the prior art at the time of filing for one of ordinary skill in the art to experimentally arrive at the claimed values from the ranges taught by the prior art. The limitations recited in the instant claims are predictable because the art teaches the rationale behind the dosages, which a skilled artisan can adjust depending upon the desired end goal disease state, as well as the structure and identity of a particular antibody. The prior art teaches ranges for the dosage, which encapsulates the fact that the art recognizes that there needs to be adjustments made to the dosage to adapt to the unique requirements of obtaining a particular disease state following treatment. As such, certain endpoints for dosage schedules, such as monthly HAE attack rates, could be routinely experimented for and determined based on the existing guidance within the prior art. A skilled artisan can experiment to obtain certain values dependent upon their end target.
Applicant argues “Office must consider the showing of unexpected results Applicant provided with its last response”. This is not found persuasive.
The antibody, dosages, and disease states of the instant invention have been taught by Panousis. Given that the structure of the antibody confers its function and the same methods are discussed, it is unclear how the Applicant received “unexpected results” when performing the same methods. Given that the composition contains the same sequences and are administered in the same methods as claimed, the prior art composition and method would inherently result in the same unexpected results, as a product and its properties are inseparable (see MPEP § 2112(I)). The Examiner does not dispute the findings supplied in the affidavit; rather, the Examiner questions the assertion of how the recited characteristics in the affidavit are not inherent to the identical antibody structures of the prior art and thus, the manner in which the instant invention circumvents the prior art.
Therefore, the rejection has been modified to reflect the amended claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SELAM BERHANE/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
