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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/26/2026 has been entered.
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, and 39-45 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, and 39-45 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. 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 75-250mg of newly amended claim 19. 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 and 45 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, and 39-45 are anticipated by Panousis et al.
Response to Arguments
Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive.
Applicant argues that “a reference must disclose all of the limitations arranged or combined in the same way as recited in the claim” and “the Office has not established that Panousis described the claimed subject matter 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 not pointed out which, if any, of the instant claims are the “missing element” that is not recited by the prior art. Panousis et al. teaches the same antibody, same range of dosages, 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. The breadth of the teachings is immaterial to the instant rejection as the recited disease from the claim is also discussed in the prior art. Moreover, although the prior art teaches that a number of diseases can be treated with the antibodies, as stated in MPEP 2131.02 - "A REFERENCE THAT CLEARLY NAMES THE CLAIMED SPECIES ANTICIPATES THE CLAIM NO MATTER HOW MANY OTHER SPECIES ARE NAMED: …when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying, "The tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is described' as that term is used in 35 U.S.C. § 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982) (The claims were directed to polycarbonate containing cadmium laurate as an additive. The court upheld the Board's finding that a reference specifically naming cadmium laurate as an additive amongst a list of many suitable salts in polycarbonate resin anticipated the claims. The Applicant had argued that cadmium laurate was only disclosed as representative of the salts and was expected to have the same properties as the other salts listed while, as shown in the application, cadmium laurate had unexpected properties. The court held that it did not matter that the salt was not disclosed as being preferred, the reference still anticipated the claims and because the claim was anticipated, the unexpected properties were immaterial."
Applicant argues “the Office impermissibly picks and chooses among Panousis’ disparate disclose in an attempt to piece together something that falls within the scope of the claim”. This is not found persuasive.
Applicant is reminded that the prior art rejection above is an anticipatory style rejection, and not an obviousness one. As such, the anticipation rejection using the Panousis reference lists out all of the claim limitations within its teachings. As stated above, the number of species in an anticipatory rejection is not a consideration when arguing against a rejection so long as the claim limitations are anticipated.
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 and how selecting a disease constitutes “impermissible picking and choosing” from the disclosure.
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 “the Office has not established inherency” as “atherosclerosis and HAE are two very different diseases that are typically treated with different classes of therapeutics”. This is not found persuasive.
As discussed above, Panousis targets the pathway that Applicant mentions on page 6 in the Remarks. At the time of the filing of the prior art, Panousis set forth the teachings that hereditary angioedema is implicated in this pathway and thus able to be a target of treatment. The instant rejection is not arguing on behalf of the treatment of atherosclerosis; rather, it references the starting point of the prior art and delves into the rationale behind the pathways that factor XII impacts. This allows the disclosure of the prior art to consider other diseases that can be treated by modulating key factors of the disease state. While Applicant claims that Panousis is silent on hereditary angioedema and that the antibody it teaches is only effective against atherosclerosis, it is clear that the antibody of Panousis would have the same characteristics as the instantly claimed antibody due to their shared structures and also because 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). 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). Since the antibody structure is well known and its function is taught in the art, the Office’s arguments regarding inherency remain as structure confers function.
Applicant argues “the claimed methods achieved unexpected clinical benefits that the industry has praised” and has submitted an affidavit on behalf of the inventor of WO 2017/173494 A1 attesting to such. 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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights