DETAILED ACTION
Examiner acknowledges receipt of applicant’s reply filed 11/07/2025, in response to the restriction requirement mailed 10/07/2025.
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 are pending.
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 are being examined on the merits in this office action.
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 .
Election/Restrictions
Applicant’s election without traverse of the following species in the reply filed on 11/7/2025 is acknowledged.
C1 esterase inhibitor: C1NH having an amino acid sequence identical or similar to the amino acid sequence of endogenous human C1 esterase inhibitor
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 read on the elected species.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
See e.g., as-filed specification at para. [0057], [0082], and [0084].
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc.
Trademark in the Specification
The use of at least the trademarks Cinryze®, Verinert®, Haegard®, Ruconest® has been noted in this application. This is not deemed to be a comprehensive list of pages and/or trademarks within the specification. They should be capitalized wherever they appear and be accompanied by the generic terminology. Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks.
See at least pages 2, 14, 20, and 24 of the specification This is not deemed to be a comprehensive list of pages and/or trademarks within the specification.
See also claim 21.
Examiner requests that applicant thoroughly review the specification for trademark terms.
Claim Objections
Claim 1 is objected to because of the following informalities:
As currently presented, claim 1 does not administer the C1INH to any patient.
Claim 1 should be amended to recite “comprising administering a therapeutically effective amount of C1 esterase inhibitor (C1INH) to a patient in need thereof”, to correlate the active step with the preamble.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 9, 12, 13, 17, 27-31, 34-40, 63 and 64 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming. The Federal Circuit has emphasized that "the hallmark of written description is disclosure" and "[t]hus, ‘possession as shown in the disclosure’ is a more complete formulation." Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. Accordingly, "the test requires an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art" and "[b]ased on that inquiry, the specification must describe an invention understandable to that skilled artisan and show that the inventor actually invented the invention claimed." Id.
The instant claims are drawn to a method of treating a patient suffering from respiratory distress, comprising administering a therapeutically effective amount of C1 esterase inhibitor (C1INH), wherein the respiratory distress is related to a coronavirus infection. Claim 15 recites wherein the C1INH has an amino acid sequence identical or similar to the amino acid sequence of endogenous human Cl esterase inhibitor. Claim 21 recites wherein the C1INH is Ruconest®.
The specification states at para. [0034]:
The terms “C1 Inhibitor,” “C1 esterase Inhibitor,” “C1-INH” and “C1INH” refer to the proteins or fragments thereof that function as serine protease inhibitors to inhibit proteases associated with the complement system, such as proteases C1r and C1s as well as MASP-1 and MASP-2; with the kallikrein-kinin system, such as plasma kallikrein and factor Xlla; and with the coagulation system, such as factor XIa. In addition, C1INH can serve as an anti-inflammatory molecule that reduces the selectins-mediated leukocyte adhesion to endothelial cells. C1INH, as used herein, can be a native serine protease inhibitor or active fragment thereof, or it can comprise a recombinant peptide, a synthetic peptide, peptide mimetic, or peptide fragment that provides similar functional properties—e.g., the inhibition of proteases C1r and C1s, MASP-1, MASP-2, factor Xlla, and/or factor XIa. C1INH, as used herein, includes both plasma-derived C1INH (e.g., purified from human plasma) and recombinantly produced C1INH (e.g., produced in rabbits or cell culture system).
Para. [0034]:Emphasis added.
Thus, the instant claim scope encompasses both treating a respiratory disease related to a coronavirus infection comprising administering a C1 esterase Inhibitor of variable composition.
The examples are limited to Ruconest® (recombinant human C1INH).
Example 1 relates to administration of Ruconest (recombinant human C1INH) to 5 patients with COVID-19 suffering from respiratory distress. Each patient was administered an initial loading dose of 8400 units of C1INH via intravenous injection. Subsequently, each patient was administered 4200 units of C1INH every twelve hours over the next three days via intravenous injection. The example discloses that four out the five patients improved significantly within one day of treatment.
Examples 2 and 3 are prophetic examples of a clinical trial of patients with SARS-CoV-2 infection who will administered Ruconest.
There are no examples of prevention. The only C1 esterase inhibitor reduced to practice was Ruconest®.
The working examples are limited to the C1 esterase inhibitor Ruconest®. The specification does not describe any other homologues, fragments or derivatives, much less what compounds have the same function as being a homologue, fragment or derivative of C1 esterase inhibitor for use in the claimed method of treating respiratory distress related to a coronavirus infection. Description of Ruconest® is not sufficient to encompass numerous other proteins, peptides and fragments of a C1 esterase inhibitors that belong to the same genus. As noted in the specification, the claimed C1 esterase Inhibitor encompass proteins or fragments of varying amino acid compositions, and numerous distinct qualities that make up the genus.
The examples of treatment are limited to Ruconest®. The skilled artisan cannot envision the functional correlations of the genus of homologues, fragments, or derivatives of Ruconest® that can be used in the claimed methods of treatment. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 are 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 treating [alleviate, ameliorate, lessen, slow down the progression or severity] a respiratory disease caused by a coronavirus infection with administration of Ruconest®, does not provide enablement for treating [prophylactic, prevent, or inhibit] a respiratory disease caused by a coronavirus infection. 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.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict-ability of the art, and (8) the breadth of the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Nature of the Invention and Breadth of the Claims
Claim 1 is drawn to a method of treating a patient suffering from respiratory distress, comprising administering a therapeutically effective amount of C1 esterase inhibitor (C1INH), wherein the respiratory distress is related to a coronavirus infection.
The claim term “respiratory distress is related to a coronavirus infection” is not expressly defined in the specification.
It is further noted that instant claim 1 does not expressly disclose that that the C1 esterase inhibitor is administered to the “patient suffering from respiratory distress”. The active method step does not relate back to the preamble (see separate claim objection above).
The specification states:
As used herein, the terms “treat,” “treatment,” “treating,” or “amelioration” when used in reference to a disease, disorder or medical condition, refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent, reverse, alleviate, ameliorate, inhibit, lessen, slow down and/or stop the progression or severity of a symptom or condition. The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition. Treatment is generally “effective” if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective” if the progression of a disease, disorder or medical condition is reduced or halted. That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation or at least slowing of progress or worsening of symptoms that would be expected in the absence of treatment. Also, “treatment” can mean to pursue or obtain beneficial results, or lower the chances of the individual developing the condition even if the treatment is ultimately unsuccessful. Those in need of treatment include those already with the condition as well as those prone to have the condition or those in whom the condition is to be prevented.
Para. [0040]. Emphasis added.
The specification states at para. [0034]:
The terms “C1 Inhibitor,” “C1 esterase Inhibitor,” “C1-INH” and “C1INH” refer to the proteins or fragments thereof that function as serine protease inhibitors to inhibit proteases associated with the complement system, such as proteases C1r and C1s as well as MASP-1 and MASP-2; with the kallikrein-kinin system, such as plasma kallikrein and factor Xlla; and with the coagulation system, such as factor XIa. In addition, C1INH can serve as an anti-inflammatory molecule that reduces the selectins-mediated leukocyte adhesion to endothelial cells. C1INH, as used herein, can be a native serine protease inhibitor or active fragment thereof, or it can comprise a recombinant peptide, a synthetic peptide, peptide mimetic, or peptide fragment that provides similar functional properties—e.g., the inhibition of proteases C1r and C1s, MASP-1, MASP-2, factor Xlla, and/or factor XIa. C1INH, as used herein, includes both plasma-derived C1INH (e.g., purified from human plasma) and recombinantly produced C1INH (e.g., produced in rabbits or cell culture system).
Para. [0034]:Emphasis added.
The specification states that “respiratory distress” refers to a condition in which a patient has to work harder to breathe and/or is not getting sufficient oxygen. Examples of objective signs of respiratory distress include, for example, increased respiratory rate, accessory muscle use, hypoxemia, hypercapnea, and lethargy (para [0035]).
Thus, the instant claim scope encompasses both treating and preventing a respiratory disease related to a coronavirus infection comprising administering a C1 esterase Inhibitor of variable composition.
State of the Prior Art
Davis et al teach (Thrombosis and Haemostasis 106:886-893 (2010)) that C1 inhibitor (C1INH) is a serpin that regulates both complement and contact (kallikrein-kinin) system activation. It consists of a serpin domain that is highly homologous to other serpins and an amino terminal non-serpin mucin-like domain (abstract). C1INH has additional anti-inflammatory functions independent of protease inhibition. These include interactions with leukocytes that may result in enhanced phagocytosis, with endothelial cells via E and P-selectins that interfere with leukocyte rolling and in turn results in suppression of transmigration of leukocytes across the endothelium, and interactions with extracellular matrix components that may serve to concentrate C1INH at sites of inflammation. In addition, C1INH suppresses gram negative sepsis and endotoxin shock, partly via direct interaction with endotoxin that interferes with its interaction with macrophages, thereby suppressing tumour necrosis factor-α and other inflammatory mediators. Id. In lung transplantation models, pre-treatment with C1INH prevented early pulmonary dysfunction and organ damage. Two clinical cases suggested that C1 inhibitor may play a role in the management of capillary leak syndrome after lung and liver transplantation. C1INH reduced cell adherence and infiltration in transplantation-related hepatic IR injury (p. 890).
Hu et al. (Nature Rev Microbiol. 19:141-154 (2021)) is review article discussing characteristics of SARS-CoV-2 and COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19) (abstract). As a novel betacoronavirus, SARS-CoV-2 shares 79% genome sequence identity with SARS-CoV and 50% with MERS-CoV24. Its genome organization is shared with other betacoronaviruses. The six functional open reading frames (ORFs) are arranged in order from 5′ to 3′: replicase (ORF1a/ORF1b), spike (S), envelope (E), membrane (M) and nucleocapsid (N) (p. 142). SARS-CoV-2 uses the same receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2)11,47. Besides human ACE2 (hACE2), SARS-CoV-2 also recognizes ACE2 from pig, ferret, rhesus monkey, civet, cat, pangolin, rabbit and dog11,43,48,49. The broad receptor usage of SARS-CoV-2 implies that it may have a wide host range, and the varied efficiency of ACE2 usage in different animals may indicate their different susceptibilities to SARS-CoV-2 infection *p. 146). Similarly to other coronaviruses, SARS-CoV-2 needs proteolytic processing of the S protein to activate the endocytic route. It has been shown that host proteases participate in the cleavage of the S protein and activate the entry of SARS-CoV-2, including transmembrane protease serine protease 2 (TMPRSS2), cathepsin L and furin. Id. To date, there are no generally proven effective therapies for COVID-19 or antivirals against SARS-CoV-2, although some treatments have shown some benefits in certain subpopulations of patients or for certain end points. Researchers and manufacturers are conducting large-scale clinical trials to evaluate various therapies for COVID-19 (p. 149). Fig. 5 indicates SARS-CoV-2 replication and potential therapeutic targets.
Yuki et al (Clin Immunol 215:108427 (2020)) teach SARS-coV-2 (a coronavirus) caused an acute atypical respiratory disease. The virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection related symptoms include fever, dry cough and dyspnea (p. 1).
Relative Skill of those in the Art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[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. 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 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
Predictability or Unpredictability of the Art
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Examiner notes that in order to prevent an infection, the skilled artisan must be apprised of patients that are at risk of developing a coronavirus infection. In contrast, in the examples relate to treatment following infection. There are no examples of prevention of infection.
Amount of Direction or Guidance Given and Presence/Absence of Working Examples
The specification does not provide sufficient guidance or direction regarding the potential prevention of a coronavirus infection in order to prevent a respiratory distress “related to a coronavirus infection”.
Example 1 relates to administration of Ruconest (recombinant human C1INH) to 5 patients with COVID-19 suffering from respiratory distress. Each patient was administered an initial loading dose of 8400 units of C1INH via intravenous injection. Subsequently, each patient was administered 4200 units of C1INH every twelve hours over the next three days via intravenous injection. The example discloses that four out the five patients improved significantly within one day of treatment.
Example 1 states: Patient selection is important, in particular regarding the stage of inflammation. The treatment time point may be a key factor associated with the efficacy of C1INH. C1INH may perform better as rescue treatment if administered earlier during the disease course.
Example 2 relates to a clinical trial to analyze the effects of C1INH on SARS-CoV-2 infection and the resulting COVID-19 disease. A controlled randomized phase 2 clinical study will be performed testing the efficacy of Ruconest®.
Example 3 relates to a clinical trial testing the effects of C1INH in COVID-19 patients suffering from respiratory distress. Patients will be administered Ruconest®.
Examiner expressly notes that Examples 2 and 3 are prophetic examples.
There are no examples of prevention. The only C1 esterase inhibitor reduced to practice was Ruconest®.
Quantity of Experimentation Necessary
Collectively, the skilled artisan is left with all required effort to determine if the claims actually provide the treatment [prevention] of respiratory distress caused by a coronavirus infection as claimed. The effort required of the skilled artisan in light of the above Wands factors is decided undue rather than a matter of routine experimentation.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
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 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 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.
The metes and bounds of claim 1 are deemed to be indefinite. The claim term “respiratory distress is related to a coronavirus infection” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how to define the relations of respiratory distress to the coronavirus infection. The metes and bounds of the phrase are unclear. For instance is the relation of respiratory distress and coronavirus infection related by the cause of the respiratory distress being caused by a coronavirus infection. Alternatively, the relation of coronavirus infection and respiratory distress may somehow indirectly related. Therefore, clarification is required to overcome the rejection.
Because claims 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 depend from indefinite claim 1 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
To overcome this rejection, Examiner recommends that claim 1 be amended to recite “wherein the respiratory distress is caused by
Claim 2 recites the limitation "the Angiotensin-Converting Enzyme 2 (ACE-2)". There is insufficient antecedent basis for this limitation in the claim.
To overcome this rejection, claim 2 should be amended to recite “coronavirus uses [[the]] Angiotensin-Converting Enzyme 2 (ACE-2)”.
Claim 21 contains the trademark/trade name Ruconest®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a C1 esterase inhibitor and, accordingly, the identification/description is indefinite.
Claims 31, 39, and 40 recites the limitations "the clinical symptoms”, “the inflammatory markers", and “the initial pathological status”. There is insufficient antecedent basis for the limitations in the respective claims.
To overcome this rejection, claims 31,39, and 40 should be amended to recite “[[the]] clinical symptoms and [[the]] inflammatory markers… of [[the]]] initial pathological status ".
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1, 9, 15, 17, 21, 27, 28, 63, and 64 is/are rejected under 35 U.S.C. 103 as being unpatentable Nuijens (U.S. 2007/0185011 -cited IDS filed 3/23/2023), as evidenced by Nuijens et al (WO01/57079- hereinafter referred to as “Nuijens 2”), in view of Elshabrawy et al (PLOS One 7(11): e50366 (2012)) and Gorbalenya et al (Nat Microbiol 5:536-544 (March 2020)).
Nuijens, Nuijens 2, and the instant application have the same named applicant, Pharming Intellectual Property B.V.
Nuijens teach administration of an effective dose of C1 esterase inhibitor (C1INH) to treat a respiratory disease, such as acute respiratory distress syndrome (ARDS) (e.g., abstract, paras. [0026]-[0029], claims 1, 10). Treatment refers to treatment of individuals who are already with the disorder as well as those susceptible to the disorder (para [0010]). “Individual” refers to any individual, both human and non-human, both young and old, both ill and asymptomatic. Id. Nuijens teach different dosing including 50U/kg and different frequencies such 8hrs, 12 hrs and 24 hrs and different periods (see figures 1, 2,3, table 2, pages 2-4). Nuijens states at para. [0026]:
These pharmaceutical compositions may be administered in a number of ways depending on whether local or systemic treatment is desired, the area to be treated and the stability of the active compound. Suitable formulations will depend on the method of administration. The pharmaceutical composition is preferably administered by parenteral administrations, such as for example by intravenous, intra-arterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or by intrathecal or intracranial administration. In a preferred embodiment it is administered by intravenous infusion. Suitable formulations for parenteral administration are known in the art and are typically liquid formulations. These liquid formulations may for example be administered by an infusion pump. The effective dose, i.e. effective concentration and frequency, will depend on the specific pharmaceutical composition which is used, the severity of the condition and the general state of the patient's health. In general, the effective dose of a pharmaceutical composition which is based on a C1INH with a shorter half-life may be found by routine optimization. A suitable starting point is the dose which is used for the equivalent pharmaceutical composition which is based on plasma-derived C1INH. A great advantage of a pharmaceutical composition of the invention is that a high initial doses may be used in treatment, which enhances the likelihood of successful treatment. This high initial dose is possible because the C1INH in the pharmaceutical composition of the invention shows a faster clearance than its natural counterpart.
Nuijens does not expressly teach or suggest that the respiratory distress is related to a coronavirus infection.
Elshabrawy et al teach that severe acute respiratory coronavirus (SARS-CoV) infection in humans results in acute respiratory distress syndrome (ARDS) (p. 1). Reemergence of SARS in humans remains a credible health threat because of the animal reservoirs. As of now, there is no effective treatment for SARS. Id. The viral Spike (S) glycoprotein plays an essential role in receptor binding and membrane fusion critical for the virus entry, and contains epitopes that elicit neutralizing Abs. The SARSCoV S protein consists of two functional domains, S1 (amino acids 12–680) and S2 (amino acids 681–1255). The receptor binding domain (RBD) (amino acids 318–510) contained within the S1 domain is required for binding to ACE-2 receptor on the cell surface and is thought to contain the majority of neutralizing epitopes. Id. Elshabrawy et al further teach human monoclonal antibodies against conserved domains of the SARS-CoV spike protein (abstract, discussion).
Gorbalenya et al teach that the coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) was caused by a coronavirus termed SARS-CoV-2 (abstract, pp. 536, 542).
It would have been obvious to one of ordinary skill in the art to administer a therapeutically effective amount of C1 esterase inhibitor (C1INH) to a patient with a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to treat the associated respiratory distress. The skilled artisan would have known that Nuijens expressly taught that C1INH could be administered to treat acute respiratory distress syndrome (ARDS). The skilled artisan would have recognized that ARDS is the respiratory disorder caused by SARS-CoV infections (see Elshabrawy et al and Gorbalenya et al). The skilled artisan would have had a reasonable expectation of success because Nuijens further taught effective amounts of C1INH for treatment, as well as routes of administration. KSR International Co. v, Teleflex inc., 127 S. Gt, 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex inc. 127 S. Ct. 1727, 1741 (2007) also discloses, "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results".
Additionally, the U.S. Federal Circuit has explicitly stated that in order to make a prima facie case of obviousness, the suggestion and motivation to combine the references need not be explicitly stated in the text of the references. In DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641 (Fed. Cir. 2006), the Court writes, “the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself. In re Dembiczak, 175 F.3d 994, 999 [50 USPQ2d 1614] (Fed. Cir. 1999). As we explained in Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 [43 USPQ2d 1481] (Fed. Cir. 1997), ‘there is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.’” See Dystar at 1645. “Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” See Dystar at 1650.
Accordingly, instant claim 1 is rendered obvious.
Regarding claim 9, Elshabrawy et al teach that the coronavirus uses cellule ACE-2 receptor for cell entry (pp. 1, 6). Regarding claim 15, Nuijens teach that C1INH has an amino acid sequence identical or similar to endogenous human C1 esterase inhibitor (e.g., para. [0031], Exs 1-3). Regarding claim 17, the C1 inhibitor has a half-life which is less than 60% of the half-life of plasma-derived C1 inhibitor. A C1INH with a shorter half-life may result in a better ratio of beneficial effects and adverse reactions. The use of proteins with a shorter half-life allows for the exposure of an individual to an active compound at a certain level for a concise predetermined time span (paras [0012]-[0016]). See also Example 2 discloses pharmacokinetics of the recombinant human C1INH which had a half-life of about 3 hours. Regarding claim 21, Nuijens teach preparation of C1INH isolated from milk of transgenic rabbits as described in WO 01/57079 [cited herein as Nuijens 2]. Nuijens 2 teaches preparation of Ruconest® in the milk of transgenic mammals. See also instant specification at para [0048]). Regarding claim 27, the C1INH is administered at a dose of more than 25 U/kg body weight of the patient (e.g., paras. [0031], Ex 1-3, claim 11). Regarding claim 28, the C1INH is administered at a dose of more than 50 U/kg body weight of the patient (e.g., paras. [0031], Ex 1-3, claim 12). Regarding claim 63, C1 esterase INH (C1INH) may be used to replace human plasma derived C1INH. C1INH may be used for the treatment of individuals suffering from any condition or disease associated with an absolute or relative deficiency of functional C1INH. Such deficiency may result in an insufficient control of C1INH on local or systemic activation of inflammatory systems involved in the pathophysiology of said conditions, including the complement and contact systems (e.g., para. [0029]). Regarding claim 64, Gorbalenya et al teach that the coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) was caused by a coronavirus termed SARS-CoV-2 (abstract, pp. 536, 542). Gorbalenya et al teach the classification of coronaviruses was largely based on serological (cross-) reactivities [reads on antibodies against SARS-CoV-2] to the viral spike protein (p. 538).
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nuijens (U.S. 2007/0185011 -cited IDS filed 3/23/2023), as evidenced by Nuijens et al (WO01/57079- hereinafter referred to as “Nuijens 2”), in view of Elshabrawy et al (PLOS One 7(11): e50366 (2012)) and Gorbalenya et al (Nat Microbiol 5:536-544 (March 2020)), as applied to claims 1, 9, 15, 17, 21, 27, 28, 63, and 64 above, and further in view of Wygrecka et al. (Am J Resp Crit Care Med 106:186-199 (2017), as evidenced by Riedl (Clin Drug Investig 35:407–417 (2015)).
Nuijens, Nuijens 2, and the instant application have the same named applicant, Pharming Intellectual Property B.V.
The teachings of Nuijens, Nuijens 2, Elshabrawy et al, and Gorbalenya et al are set forth above.
While Nuijens teach treating ARDS with C1NH, and Elshabrawy et al and Gorbalenya et al teach that SARS-CoV/ SARS-CoV-2 infection cause ARDS, the references do not explicitly teach ventilators as being associated with the treatment of ARDS, or a decrease in clinical symptoms/ inflammatory markers.
Wygrecka et al. teach that acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by an acute onset, bilateral opacities following chest imaging, pulmonary edema, and severe hypoxemia. Etiologically, ARDS can result from several direct and indirect causes. Reducing the detrimental effects of ventilation currently represents the most important measure taken to combat the effects of ARDS. ARDS may resolve completely after the acute phase or culminate in pathologic tissue remodeling and fibrotic alteration of the lung. ARDS has a poor prognosis and no specific treatment. Reducing the detrimental effects of ventilation currently represents the most important measure taken to combat the effects of ARDS (p. 187). Wygrecka et al. teach that 46 patients with moderate to severe ARDS were investigated (direct ARDS, n = 28; indirect ARDS, n = 18). Id.
Wygrecka et al. teach the effect of C1INH administration on fibrin formation in vivo. However, no changes in fibrin(ogen) and D-dimer levels and the BALF clotting time between bleomycin-treated animals that received C1INH and those that obtained vehicle were observed (Figures 2A–2D) (pp. 187-188). Wygrecka et al. teach that importantly, administration of C1INH into bleomycin-challenged B1-/-/B2-/- animals preserved lung structure; reduced leukocyte and neutrophil counts in BALF; and diminished TNF-a, IL-1b, and IL-6 expression as compared with B1-/-/B2-/- littermates receiving vehicle (Figures 2F–2H, 2K, 2L, and E3C). This indicates that C1INH may attenuate inflammatory responses independently of the kallikreinkinin system (p. 192). Application of C1INH or antihistone antibodies (αHis) conferred cytoprotection; however, when given simultaneously no additive effect was observed implying that C1INH and αHis use a similar mechanism to prevent cell death (Figures 3B and 3C). The protective effect of C1INH was dose dependent and did not rely on its protease inhibitory activity because reactive center-cleaved C1INH (iC1INH) and heat denatured C1INH were able to block histone- or NET-mediated cell death (Figures 3D and 3E). Moreover, the cytoprotective effect of C1INH, iC1INH, and denatured C1INH was also observed when primary mouse alveolar type II cells and human lung microvascular endothelial cells were exposed to histones or NET (Figures 3F and 3G) (pp. 192, 196-197).
Riedl evidences that C1 esterase inhibitor (C1-INH) is administered to patients suffering from respiratory distress at 50 IU/kg with 2 doses every 24 hrs. This is a routine dosage routine approved by the FDA in 2014. Although the frequency of attacks can vary considerably in untreated patients (every 7–14 days on average), individual HAE attacks generally follow a predictable clinical course of symptoms developing gradually during the first 24 h and then subsiding during the subsequent 48–72 h (Table 1; p.p 408-409). Thus teaching an administration routine for at least 96 hours.
It would have been prima facie obvious to one skilled in the art to combine the teachings of above references because Wygrecka et al. teach that ARDS is a life-threatening condition characterized by an acute onset and administration of C1INH preserved lung structure in animal models. Nuijens teach the C1 inhibitor (C1INH) with shorter half-life than plasma-derived C1 inhibitor for the preparation of a medicament for the treatment of an individual with ARDS. Nuijens provides therapeutically effective amounts of C1INH, routes of administration, dosing regimens, as well as guidance for assessing treatment. Elshabrawy et al and Gorbalenya et al teach that SARS-CoV/ SARS-CoV-2 infection cause ARDS. It would have been obvious to the skilled artisan to administer a therapeutically effective amount of C1INH to a patient suffering from ARDS related to a SARS-CoV-2 infection. No more than routine skill is required to administer the well known dosage routine for C1INH. The benefit of combining references be a better method of treating and preventing damage by the ARDS to lungs as taught by Wygrecka et al. Furthermore, the limitations every eight or twelve hours, for a period of at least 72 or 96 hours, this would be considered optimization of experimental parameters and would be obvious to one of ordinary skill in the art, especially when the prior art teach a the well known dosage scheme for the well known C1INH. However, where 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, 220 F.2d 454, 456, 105 USPQ 233, 235(CCPA 1955).
Additionally, KSR International Co. v, Teleflex inc., 127 S. Gt, 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex inc. 127 S. Ct. 1727, 1741 (2007) also discloses, "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Accordingly, claims 29, 30, and 34-38 are rendered obvious. It is further noted that Riedl provides dosing guidance based on a patient weight of more or less than 84 kg.
Regarding claims 12 and 13, Wygrecka et al. teach that ARDS patients often require ventilators/ventilation (pp. 187, 193-194). Administration of C1INH before or after the patient is on a ventilator is deemed to be routine optimization on the part of the skilled artisan, e.g., medical professional.
Regarding claims 31, 39, and 40, the selection of C1INH dosage amount/timing to achieve the recited the goal of a decrease of clinical symptoms/inflammatory markers by 50% of the initial pathological status or reached normal values would have been a routine matter of optimization on the part of the artisan of ordinary skill. Said artisan recognizing that Wygrecka et al. teach administration of C1INH resulted in improved clinical symptoms and a decrease in inflammatory markers- e.g., macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF)-α, IL-1β, and neutrophil chemoattractant (KC) expression on the mRNA and/or protein level. The reference further taught methods/assays for assessing inflammatory marker levels. A holding of obviousness over the cited claims is therefore clearly required.
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 are rendered obvious in view of the teachings of the cited references.
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, 15, 17, 21, 27, 28, and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-30 of copending Application No. 18577708 (hereinafter referred to “the ‘708 application), in view of Elshabrawy et al (PLOS One 7(11): e50366 (2012)), Gorbalenya et al (Nat Microbiol 5:536-544 (March 2020)), and Nuijens (U.S. 2007/0185011 -cited IDS filed 3/23/2023).
This is a provisional nonstatutory double patenting rejection.
Claim 16 of the ‘708 application recites a method for treating a patient suffering from neurological symptoms related to a viral infection, the method comprising administering a therapeutically effective amount of a C1 esterase inhibitor (C1INH) to the patient. Claim 18 of the ‘708 application recites wherein the neurological symptoms are related to COVID-19 and/or wherein the viral infection is a coronavirus infection, wherein the coronavirus preferably is SARS-CoV-2.
The claims of the ‘708 application do not explicitly recite that the patient with a coronavirus infection is suffering from respiratory distress.
Elshabrawy et al teach that severe acute respiratory coronavirus (SARS-CoV) infection in humans results in acute respiratory distress syndrome (ARDS) (p. 1). Reemergence of SARS in humans remains a credible health threat because of the animal reservoirs. As of now, there is no effective treatment for SARS. Id. Gorbalenya et al teach that the coronavirus-associated acute respiratory disease (SARS) called coronavirus disease 19 (COVID-19) was caused by a coronavirus termed SARS-CoV-2 (abstract, pp. 536, 542).
Nuijens expressly taught administration of C1INH to treat ARDS (abstract, paras. [0026]-[0029], claims 1, 10).
It would have been obvious to one of ordinary skill the art to administer the C1INH of the ‘708 application to a person with a coronavirus infection suffering from respiratory disease. The skilled artisan would have known from Elshabrawy et al and Gorbalenya et al that a patient with a SARS-CoV infection would likely be suffering from respiratory distress because the coronavirus was the causative agent of severe acute respiratory syndrome (SARS/ARDS). The skilled artisan would have had a reasonable expectation of success because Nuijens expressly taught administration of C1INH to treat ARDS (abstract, paras. [0026]-[0029], claims 1, 10).
Accordingly, claim 1 is rendered obvious.
Regarding claim 15, claim 21 of the ‘708 application recites wherein the patient is a human and/or wherein the C1INH has an amino acid sequence at least 70% identity to the amino acid sequence of endogenous human C1INH.
Regarding claim 17, claim 22 of the ‘708 application recites wherein the C1INH has a plasma half-life of less than six hours.
Regarding claim 21, claim 24 of the ‘708 application recites wherein the C1INH is Ruconest®.
Regarding claims 27 and 28, claim 26 of the ‘708 application recites wherein the C1INH is administered at a dose of at least about 25 U/kg body weight of the patient, or wherein the C1INH is administered at a dose of at least about 50 U/kg body weight of the patient.
Regarding claim 64, claim 19 of the ‘708 application recites that the patient has antibodies against SAR-CoV-2.
Conclusion
No claims are allowed.
Claims 1, 9, 12, 13, 15, 17, 21, 27-31, 34-40, 63 and 64 are pending and are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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, LIANKO GARYU can be reached at 571-270-7367. 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.
/KRISTINA M HELLMAN/Examiner, Art Unit 1654