DETAILED ACTION
Acknowledgment and entry of the Amendment submitted on 1/26/26 is made.
Claims 17-18 have been canceled
Applicants previously elected without traverse the Species:
1) The immunomodulatory agent capable of binding the infectious agent in claim 18: a probiotic strain;
2) the infectious agent: Pseudomonas aeruginosa;
3) the agent capable of binding an infectious agent: an antibody.
in the reply filed on 10/6/25.
Claims 16 and 19-35 are currently pending and under examination.
Claim Rejections - 35 USC § 112-2nd paragraph
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 16 and 19-35 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.
Claim 16 and 34 are vague and indefinite because the subject matter for which protection is sought (the therapeutic agents to be used in the method) is not clearly defined. The claims have been amended to include a long laundry list of generic compounds, e.g., administering to the subject at least one agent capable of binding an-a respiratory infectious agent selected from the group consisting of an antibody, a bispecific antibody, a multispecific antibody, an antibody fragment, a single domain antibody, a unibody, a nanobody, an affibody, an affilin, an affitin, an adnectin, an atrimer, a DARPin, an anticalin, an avimer, a fynomer and a versabody, and at least one immunostimulatoryimmunomodulatory agent selected from the group consisting of a probiotic strain, a mixture of probiotic strains, a Toll-like receptor agonist, a NOD-like receptor agonist, a RIG-like receptor agonist, a cytokine or mixture of cytokines, a chemokine or mixture of chemokines, an adjuvant, a flagellin, a flagellin variant, a polypeptide comprising one or more flagellin fragment(s), a CpG oligodeoxynucleotide (CpG ODN), α-galactosylceramide (α-Gal-Cer), aluminum salts, MF59, AS03, polyinosinic- polycytidylic acid, a polyphosphazene, an antibody directed against immune checkpoints, and mixtures thereof, wherein the at least one agent capable of binding the respiratory infectious agent is administered by inhalation. The claim should provide any structural properties, for these agents which would allow for one to identify them without ambiguity. The mere vague description does not adequately define the agents. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. It is noted that the Species which was originally elected is: the agent capable of binding an infectious agent: an antibody. The claims now contain an improper Markush grouping. See below.
Claim 16 is now rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the long list of different compounds is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: these are completely different products with different structures and different effects.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single substanial structural similarity as well as a common use.
Claim Rejections - 35 USC § 112-Deposit Information
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification lacks complete deposit information for the deposit of the strains deposited at the Collection Nationale de Cultures de Microorganismes (CNCM) on April 14, 2015 under numbers CNCM I-4967 and CNCM I-4968, or the strain deposited on April 16, 2018 under number CNCM I-5314. Because it is not clear that the properties of the strains are known and publicly available or can be reproducibly isolated from nature without undue experimentation and because the best mode disclosed by the specification requires the use of the plasmids, a suitable deposit for patent purposes is required.
If the deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of the deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State. Amendment of the specification to recite the date of the deposit and the complete name and full street address of the depository is required.
qIf the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed.
Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR §1.801-1.809 for further information concerning deposit practice.
Response to Applicants’ arguments:
The Deposit certificates that are in French were received on May 2, 2023; however, the affidavit/statement, see below, has not been received.
If the deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of the deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
Claim Rejections - 35 USC § 112-Written Description
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 16 and 19-35 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.
The amendment to the claims necessitated this amendment. Claims 16 and 34 now recite a long laundry list of generic compounds, e.g., a method for treating or preventing any respiratory infection comprising administering to the subject at least one agent capable of binding any respiratory infectious agent selected from the group consisting of an antibody, a bispecific antibody, a multispecific antibody, an antibody fragment, a single domain antibody, a unibody, a nanobody, an affibody, an affilin, an affitin, an adnectin, an atrimer, a DARPin, an anticalin, an avimer, a fynomer and a versabody, and at least one immunostimulatoryimmunomodulatory agent selected from the group consisting of a probiotic strain, a mixture of probiotic strains, a Toll-like receptor agonist, a NOD-like receptor agonist, a RIG-like receptor agonist, a cytokine or mixture of cytokines, a chemokine or mixture of chemokines, an adjuvant, a flagellin, a flagellin variant, a polypeptide comprising one or more flagellin fragment(s), a CpG oligodeoxynucleotide (CpG ODN), α-galactosylceramide (α-Gal-Cer), aluminum salts, MF59, AS03, polyinosinic- polycytidylic acid, a polyphosphazene, an antibody directed against immune checkpoints, and mixtures thereof, wherein the at least one agent capable of binding the respiratory infectious agent is administered by inhalation.
The respiratory infectious agent is not recited in the claims.
Respiratory infections include a wide range of viral and bacterial illnesses affecting the upper and lower respiratory tracts, from the common cold to pneumonia and tuberculosis.
Upper Respiratory Infections (URIs)
These infections affect the nose, throat, pharynx, larynx, and bronchi. Common examples include:
Common Cold (Nasopharyngitis) – caused mainly by rhinoviruses; symptoms include sneezing, runny nose, sore throat, and mild fever.
Sinusitis – inflammation of the sinuses, caused by viruses, bacteria, or fungi.
Pharyngitis (Sore Throat) – often viral, sometimes bacterial (e.g., Group A Streptococcus),.
Laryngitis – inflammation of the larynx, usually viral.
Tonsillitis – infection of the tonsils, can be viral or bacterial.
Whooping Cough (Pertussis) – bacterial infection caused by Bordetella pertussis, highly contagious.
Influenza (Flu) – viral infection affecting the upper and sometimes lower respiratory tract.
Respiratory Syncytial Virus (RSV) – common in infants and young children, can affect both upper and lower tracts.
COVID-19 – caused by SARS-CoV 2, affecting both upper and lower respiratory tracts.
Lower Respiratory Infections (LRIs)
These infections affect the lungs and lower airways, often more severe:
Bronchitis – inflammation of the bronchi, can be acute (usually viral) or chronic (often due to smoking or COPD),.
Pneumonia – infection of the lungs, caused by bacteria (e.g., Streptococcus pneumoniae), viruses, or fungi.
Tuberculosis (TB) – bacterial infection caused by Mycobacterium tuberculosis, primarily affecting the lungs.
Mycoplasma pneumonia – atypical bacterial pneumonia, often mild but contagious.
Pulmonary infections from coronaviruses – other than COVID-19, can cause pneumonia or bronchitis
The claim also recites a laundry list of generic binding agents and immunostimulatory agents and the type or causative agent of the respiratory infection is not even recited in the claims.
There is insufficient written description for these claims. To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. Applicants have not described the genus of claimed binding agents or immunostimulatory agents such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar,935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).Furthermore, the written description provision of 35 USC § 112 is severable fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The nucleic acid [product] itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description" Requirement (66 FR 1099-1111, January 5,2001) state, "[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention" (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus'" (Id. at 1106);accordingly, it follows that an adequate written description of a genus cannot beachieved in the absence of a disclosure of at least one species within the genus.
The scope of the claim includes numerous structural variants and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe any members of the claimed genus by complete structure. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
There are no drawings or structural formulas disclosed of the sequences of these antibodies or proteins. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testingwhich of those agents would possess the necessary function. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed Genus.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. 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 (Fed. Cir. 1997); In re Gostelli, 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.
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 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (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.
MPEP § 2163 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 does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. 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 species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2dat 1012, 10 USPQ2d at 1618.
Since the MPEP states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is ''not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.'1 MPEP § 2163. Elere, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure beyond those disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance.
The description requirement of the patent statue 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.
Claim Rejections - 35 USC § 112- Scope of Enablement
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 16 and 19-35 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:
A method of treating a respiratory infection caused by Pseudomonas aeruginosa in a subject comprising administering an anti-Pa antibody mAb166 as an inhaled agent which is capable of binding an infectious agent with the administration of a mixture of CNCM I-4967 and CNCM I-4968 probiotic strains or of one of the CNCM I-4967, CNCM I-4968 or CNCM I-5314 strains;
does not reasonably provide enablement for:
A method of treating or preventing a respiratory infection in a subject, wherein the method comprises administering at least one agent capable of binding an infectious agent and at least one immunomodulatory agent to the subject, wherein the at least one agent capable of binding the infectious agent is administered by inhalation.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The examples in the instant specification do not render it either credible or plausible that any agent which is capable of binding to any infectious agent administered in combination with any immunomodulatory agent is capable of being efficacious in the treatment or prevention of any respiratory infection in a subject. The instant specification only shows the anti-Pa antibody mAb166 used as an inhaled agent which is capable of binding an infectious agent with the administration of a mixture of CNCM 1-4967 and CNCM-4968 probiotic strains or of one of the CNCM I-4967, CNCM I-4968 or CNCM I-5314 strains appears to have an effect on the treatment or prevention of a respiratory infection caused by P. aeruginosa. In the example, the Pseudomonas aeruginosa PA103 strain was used as representative of the strains involved in acute respiratory infections. Mice were infected. Two hours beforehand, the mice had received a pulmonary administration of the mAb166 antibody (murine IgG2b specific for the pcrV protein). No other antibody or "agent which is capable of binding an infectious agent" was administered. For the treatment of the mice with probiotic strains, the CNCM I-4967 and CNCM I-4968 strains, derived from naive mouse lungs and deposited with the CNCM on 14 April 2015, were used. The CNCM 1-4967 and CNCM 1-4968 strains are probiotic strains belonging to the Lactobacillaceae rhamnosus and Lactobacillaceae salivarius species, respectively, or to species that are close in genomic terms. The CNCM I-5314 strain was also used. No other probiotic or "immunomodulatory agent" was administered. The mice received either a mixture of the CNCM 1-4967 and 4968 probiotic strains or the CNCM-I-4967, CNCM-I-4968 or CNCM-I-5314 strains, intranasally 1, 2 and 3 days before the priming.
In the example, the Pseudomonas aeruginosa PA103 strain was used as representative of the strains involved in acute respiratory infections. Mice were infected. Two hours beforehand, the mice had received a pulmonary administration of the mAb166 antibody (murine IgG2b specific for the pcrV protein). No other antibody or "agent which is capable of binding an infectious agent" was administered. For the treatment of the mice with probiotic strains, the CNCM I-4967 and CNCM I-4968 strains, derived from naive mouse lungs and deposited with the CNCM on 14 April 2015, were used. The CNCM 1-4967 and CNCM 1-4968 strains are probiotic strains belonging to the Lactobacillaceae rhamnosus and Lactobacillaceae salivarius species, respectively, or to species that are close in genomic terms. The CNCM I-5314 strain was also used. No other probiotic or "immunomodulatory agent" was administered. The mice received either a mixture of the CNCM 1-4967 and 4968 probiotic strains or the CNCM-I-4967, CNCM-I-4968 or CNCM-I-5314 strains, intranasally 1, 2 and 3 days before the priming.
The effect demonstrated in the Examples set forth in the specification do not clearly reflect the much broader methods and compositions recited in the methods as claimed. Therefore, the claims are not supported by the instant specification.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
The respiratory infectious agent is not recited in the claims.
Respiratory infections include a wide range of viral and bacterial illnesses affecting the upper and lower respiratory tracts, from the common cold to pneumonia and tuberculosis.
Upper Respiratory Infections (URIs)
These infections affect the nose, throat, pharynx, larynx, and bronchi. Common examples include:
Common Cold (Nasopharyngitis) – caused mainly by rhinoviruses; symptoms include sneezing, runny nose, sore throat, and mild fever.
Sinusitis – inflammation of the sinuses, caused by viruses, bacteria, or fungi.
Pharyngitis (Sore Throat) – often viral, sometimes bacterial (e.g., Group A Streptococcus),.
Laryngitis – inflammation of the larynx, usually viral.
Tonsillitis – infection of the tonsils, can be viral or bacterial.
Whooping Cough (Pertussis) – bacterial infection caused by Bordetella pertussis, highly contagious.
Influenza (Flu) – viral infection affecting the upper and sometimes lower respiratory tract.
Respiratory Syncytial Virus (RSV) – common in infants and young children, can affect both upper and lower tracts.
COVID-19 – caused by SARS-CoV 2, affecting both upper and lower respiratory tracts.
Lower Respiratory Infections (LRIs)
These infections affect the lungs and lower airways, often more severe:
Bronchitis – inflammation of the bronchi, can be acute (usually viral) or chronic (often due to smoking or COPD),.
Pneumonia – infection of the lungs, caused by bacteria (e.g., Streptococcus pneumoniae), viruses, or fungi.
Tuberculosis (TB) – bacterial infection caused by Mycobacterium tuberculosis, primarily affecting the lungs.
Mycoplasma pneumonia – atypical bacterial pneumonia, often mild but contagious.
Pulmonary infections from coronaviruses – other than COVID-19, can cause pneumonia or bronchitis
The claim also recites a laundry list of generic binding agents and immunostimulatory agents and the type or causative agent of the respiratory infection is not even recited in the claims.
Response to Applicants arguments of the Scope of Enablement rejection:
Applicants argue:
In its argument, the Office Action merely stated that the content of the examples did not make it credible or plausible that a therapeutic effect would be generated with (i) any agent capable of binding to any infectious agent, in combination with (ii) any immunomodulatory agent, in the prevention of any respiratory infection in a subject. However, the Office Action does not provide technical justification for this position. The Applicant notes that since at least one embodiment of the invention is described in detail, and provided that the description sets out the features essential to the execution of the invention in sufficient detail for a person skilled in the art to carry out the invention, the subject matter of the claims is supported by the description on its entire scope of protection. The agent capable of binding an infectious agent previously being indefinite and thus covering too many possibilities in relation to the disclosure of the description of the application as filed according to the Office Action is now limited to an agent capable of binding a respiratory infectious agent selected from an antibody, a bispecific antibody, a multispecific antibody, an antibody fragment, a single-domain antibody, a unibody, a nanobody, an affibody, an affilin, an affitin, an adnectin, an atrimer, a DARPin, an anticalin, an avimer, a fynomer, and a versabody. The scope of protection thus has been reduced and the example of the description using the antibody mAb166 is therefore even more convincing for the support of the reduced scope of protection concerning the agent capable of binding a respiratory infectious agent. b) Since the desired therapeutic effect is against a target infectious agent responsible for respiratory infection, obtaining above cited antibodies, antibody derivatives, or antibody mimetics capable of binding to this infectious agent is now routine work for those skilled in the art. In fact, the examples as filed provide an illustration of a therapeutic effect against the infectious agent Pseudomonas aeruginosa, generated by the use, in combination with various b) Since the desired therapeutic effect is against a target infectious agent responsible for respiratory infection, obtaining above cited antibodies, antibody derivatives, or antibody mimetics capable of binding to this infectious agent is now routine work for those skilled in the art. In fact, the examples as filed provide an illustration of a therapeutic effect against the infectious agent Pseudomonas aeruginosa, generated by the use, in combination with various immunostimulatory agents, of an antibody directed against this infectious agent (in this case, the monoclonal antibody mAb166). It goes without saying that this experimental illustration can be easily adapted by those skilled in the art, depending on the infectious agent targeted, by choosing an antibody (or derivative or mimetic of this antibody) directed against the said infectious agent targeted. c) Furthermore, the examples illustrate a plurality of immunostimulatory agents that can be used in accordance with the claimed invention, and in particular illustrate the use of a plurality of distinct probiotic strains (Examples 1 to 3) and flagellin (Example 3). The results of the examples illustrate both the prophylactic effects (see Example 1) and the therapeutic effects (see Examples 2 and 3) of combining an antibody capable of binding to the infectious agent with the immunostimulatory agent. Also, numerous agents are cited in the description, for example, from paragraphs [0078] to [0153].
Moreover, the immunostimulatory agent previously being indefinite and thus covering too many possibilities in relation to the disclosure of the description of the application as filed according to the Office Action is now limited to immunostimulatory agent selected from the group consisting of a probiotic strain, a mixture of probiotic strains, a Toll-like receptor agonist, a NOD- like receptor agonist, a RIG-like receptor agonist, a cytokine or mixture of cytokines, a chemokine or mixture of chemokines, an adjuvant, a flagellin, a flagellin variant, a polypeptide comprising one or more flagellin fragment(s), a CpG oligodeoxynucleotide (CpG ODN), α-galactosylceramide (α-Gal-Cer), aluminum salts, MF59, AS03, polyinosinic-polycytidylic acid, a polyphosphazene, an antibody directed against immune checkpoints, and mixtures thereof. The scope of protection thus has been reduced and the example of the description using the antibody flagellin or probiotic strains are therefore even more convincing for the support of the reduced scope of protection concerning the immunostimulatory agent. d) In order to facilitate the examination procedure for the granting of the patent and to support its arguments, Applicant provides the experimental results presented in Figures 8 and 9 and the following observations.
Applicants’ arguments have been fully and carefully considered but are not deemed persuasive.
First, Applicants arguments are directed to non-elected species, which are rejected as being in an Improper Markush grouping, and are different inventions. Applicants elected without traverse the Species:
1) The immunomodulatory agent capable of binding the infectious agent in claim 18: a probiotic strain;
2) the infectious agent: Pseudomonas aeruginosa;
3) the agent capable of binding an infectious agent: an antibody.
With respect to this elected combination, A method of treating a respiratory infection caused by Pseudomonas aeruginosa in a subject comprising administering an anti-Pa antibody mAb166 as an inhaled agent which is capable of binding an infectious agent with the administration of a mixture of CNCM I-4967 and CNCM I-4968 probiotic strains or of one of the CNCM I-4967, CNCM I-4968 or CNCM I-5314 strains; is the only evidence provided in the specification for treating the respiratory infection caused by the infectious agent: Pseudomonas aeruginosa. Applicants’ arguments on treatment of H3N2 influenza virus with a different, antibody CR9114 and flagellin, does not enable treating the elected invention. It is a completely different invention. The scope of the instant claims is unduly broad and the Markush Grouping is improper as recited in the 112, 2nd paragraph rejection. This additional information does not, for instance, enable the breadth of the instant claims. Treating H3N2 influenza versus P. aeruginosa or Covid-19 or Bordetella pertussis or M. tuberculosis, etc. are completely different inventions which utilize completely different agents of treatment that are not predictable among the different virus and bacterial pathogens.
Prior art rejections
NOTE: Independent claims 16 and 34 relate to a method of treating or preventing a respiratory infection comprising administering a combination of an agent which is capable of binding an infectious agent and of at least one immunomodulatory agent, for use thereof in the treatment or prevention of a respiratory infection. Neither the agent which is capable binding an infectious agent nor the immunomodulatory agent is clearly defined (see 112, 1st and 2nd paragraph rejections set forth above), e.g., the generic use of ‘antibody’ or unibody with not associated structure, etc. does not adequately definite the composition to be used in the treatment methods. Accordingly, any agent which is capable of binding any respiratory infectious agent is included in the scope of the claimed subject matter. Any agent which has any effect in immune reactions is included in the claimed subject matter.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 16 and 22-35 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Digiandomenico et al (WO 2013/070615; provided by Applicants).
Digiandomenico describes an antibody which binds to Pseudomonas PcrV for preventing or treating a respiratory infection caused by Pseudomonas aeruginosa, in combination with antibiotic. A bispecific antibody which binds to Psl and PcrV is also described and used. Administration of the antibody by inhalation is described. See Paragraph [0274] Methods of preparing and administering anti-Pseudomonas Psl and/or PcrV binding molecules, e.g., an antibody or fragment, variant or derivative thereof, as disclosed herein to a subject in need thereof are well known to or are readily determined by those skilled in the art. The route of administration of the anti-Pseudomonas Psl and/or PcrV binding molecules, e.g., antibody or fragment, variant or derivative thereof, can be, for example, oral, parenteral, by inhalation or topical. The term parenteral as used herein includes, e.g., intravenous, intraarterial, intraperitoneal, intramuscular, or subcutaneous administration. It is indicated that the antibody in question can be conjugated to an antimicrobial agent, a therapeutic agent, a lymphokine (a subset of cytokines) or a heterologous antibody. Claims 66 and 67 recite either sequential or simultaneous administration of the antibody and the immunomodulatory agent. Paragraph [0019] recites that the method of preventing or treating may be of a Pseudomonas infection. Pseudomonas infection in a subject in need thereof, comprising administering to the subject an effective amount of a composition described herein, wherein said administration provides a synergistic therapeutic effect in the prevention or treatment of the Pseudomonas infection in said subject, and wherein said synergistic effect is greater than the sum of the individual effects of administration of equal molar quantities of the individual binding domains. In one embodiment, the synergistic therapeutic effect results in greater percent survival than the additive percent survival of subjects to which only one of the binding domains has been administered. In one embodiment, the composition is administered for two or more prevention/treatment cycles. In one embodiment, the binding domains or binding molecules are administered simultaneously. In one embodiment, the binding domains or binding molecules are administered sequentially. In one embodiment, the Pseudomonas infection is a P. aeruginosa infection. In one embodiment, the subject is a human. In one embodiment, the infection is an ocular infection, a lung infection, a burn infection, a wound infection, a skin infection, a blood infection, a bone infection, or a combination of two or more of said infections. In one embodiment, the subject has acute pneumonia, burn injury, corneal infection, cystic fibrosis, or a combination thereof.
With respect to Applicants’ arguments:
The term ‘immunostimulatory agent’ is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. A lymphokine such as taught in the prior art references meets the structural limitations.
Claim(s) 16 and 22-35 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Sellman et al (WO 2015/196011; provided by Applicants).
Sellman describes the combined administration of an antibody which binds to a P. aeruginosa antigen and of another antibacterial agent for the treatment of respiratory infections caused by P. aeruginosa. The other antibacterial agent can be an antibiotic. Administration of the antibody by inhalation is described. See paragraph [0014], antibody binding to P. aeruginosa. Paragraph [0142] recites methods of preparing and administering anti-bacterial antibodies or antigen- binding fragments thereof (e.g. anti-Staphylococcus, anti-51. aureus, anti-alpha toxin, anti- Pseudomonas, anti-P. aeruginosa, anti-Psl, anti-PcrV, or anti-Psl and PcrV antibodies, or antigen-binding fragments thereof) are well known to or are readily determined by those skilled in the art. The route of administration of the anti-bacterial antibodies or antigen- binding fragments thereof can be, for example, oral, parenteral, by inhalation or topical. Paragraph [0144] In certain embodiments, anti-bacterial antibodies or antigen-binding fragments thereof (e.g. ^^-Staphylococcus, anti-51. aureus, anti-alpha toxin, anti-Pseudomonas, anti-P. aeruginosa, anti-Psl, anti-PcrV, or anti-Psl and PcrV antibodies or antigen-binding fragments thereof) can be used in combination with other anti-bacterial agents such as antibiotics. Antibiotics include, for example, beta-lactam antibiotics (such as cephalexin), sulfa drugs (like co-trimoxazole/trimethoprim-sulfamethoxazole), tetracyclines (like doxycycline and minocycline), clindamycin, vancomycin, linezolid, daptomycin, teicoplanin, quinupristin/dalfopristin (synercid), tigecycline, ciprofloxacin, meropenem, tobramycin, and aztreonam. In certain embodiments, the antibiotic is ciprofloxacin. [0063] An "effective amount" of an antibody or immunoconjugate as disclosed herein is an amount sufficient to carry out a specifically stated purpose. [0064] Administration "in combination with" one or more further therapeutic agents include simultaneous (concurrent) and consecutive administration in any order. [00128] The pharmaceutical preparations routinely contain salts, buffering agents, preservatives, compatible carriers, and optionally other therapeutic agents.
With respect to Applicants’ arguments:
The reference allows for other therapeutic agents that include ‘salts.” The term ‘immunostimulatory agent’ is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 16 and 19-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Digiandomenico et al (WO 2013/070615; provided by Applicants) and Sellman et al (WO 2015/196011; provided by Applicants) in view of Geanncarlo et al (FR 3,094,378, October 2020; provided by Applicants), Lacoste et al (FR 2,917,623, December 2008; provided by Applicants), Remot et al (The Isme J. Multidisciplin. J. Microbial Ecology. Jan. 2017. 11(5): 1061-1074; provided by Applicants) or Villena et al (Internat. Immunopharmac. Elsevier, Amsterdam, NL. 11(11): 1633-1645; provided by Applicants).
The teachings of Digiandomenico and Sellman are set forth above. However, they do not particularly exemplify disclose the combination of the antibody with a probiotic strain or a mixture of probiotic strains selected from the family of Lactobacillaceae.
Geanncarlo et al relates to the identification of bacteria of the pulmonary microbiota which are capable of modifying the immune response during Mycobacterium tuberculosis infection. Among these bacteria, three are lactobacilli (L. salivarius, L. animalis and L. rhamnosus) which have a GRAS (Generally Recognised As Safe) organism status and have been deposited with the CNCM [French National Microorganism Culture Collection] under numbers: CNCM I 4968, CNCM I 5314 and CNCM I 4967, respectively. The three lactobacilli isolated from the pulmonary microbiota have strong immunomodulatory capacities, with an anti-inflammatory profile (even outside an infectious context). The use of an L. animalis strain (CNCM I-5314 is preferred) for use thereof in the treatment and/or prevention of inflammation related to a respiratory disease is claimed. The advantage of such a use compared to the use of antibiotics in the context, for example, of a P. aeruginosa infection is indicated.
Lacoste describes the use of Lactobacillus bacteria (Lactobacillus rhamnosus) for producing a medicament intended to prevent or delay the colonization of a patient's respiratory system by pathogenic bacteria, preferably Pseudomonas aeruginosa.
Remot describes the isolation of Lactobacillaceae CNCM I 4967 and CNCM I 4968 from mouse lungs. The use of probiotics for pulmonary immunity in the treatment of pulmonary diseases is suggested.
Villena describes the use of lactic acid bacteria in the treatment of respiratory infections, and the immunomodulatory effect thereof. The use of said bacteria is particularly important in immunocompromised individuals.
It would have been prima facie obvious for one of ordinary skill in the art to add a probiotic strain, and more specifically from the Lactobacillaeceae family, and more specifically from strains CNCM I 5314, CNCM I 4968 and/or CNCM I 4967, to the antibody compositions taught by Digiandomenico and Sellman because it would have been obvious as indicated in the prior art that administration with another immunomodulatory agent would have a greater effect in the treatment of respiratory pathological conditions caused by P. aeruginosa.
Instant claim 16 recites that the immunostimulatory agent may be any probiotic strain or a mixture of any probiotic strains.
With respect to Applicants’ arguments:
The term ‘immunostimulatory agent’ is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. A probiotic strain such as taught in the prior art references meets the structural limitations.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicants argue:
Applicant, however, disagrees with such assertion. Combining two treatments may have negative effects, for example, one treatment may cancel out the effects of the other one. Furthermore, choosing a particular combination is not necessarily obvious, since the effects of each treatment may not add up or may add up without synergy. The Applicant selected two specific treatments from a list of treatments for the same disease, not arbitrarily but because, as indicated by the test results given in the examples in the application, a beneficial and unexpected synergistic effect is obtained with the combination of these two treatments. Such a beneficial effect is illustrated in the application with the combination of mAb166+ immunostimulatory agent and now also in Appendix A with CN9114+ immunostimulatory agent.
These arguments re not commensurate in scope with the claimed invention.
Further, the Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claim(s) 16 and 19-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karine et al (J. Immune Based Therapies and Vaccines, Biomed Centeral LTD., London, GB Vol. 1 No. 1August 2003, pp. ; provided by Applicants) in view of Geanncarlo et al (FR 3,094,378, October 2020; provided by Applicants), Remot et al (The Isme J. Multidisciplin. J. Microbial Ecology. Jan. 2017. 11(5): 1061-1074; provided by Applicants) and Lucie et al ("Use of lung microbiota strains to shape local immunity at steady state and during Mycobacterium tuberculosis infection in the mouse model". , 13 January 2020 (2020-01-13), XP055882634. Retrieved from the Internet: URL:chrome-extension:// efaidnbmnnnibpcajpcglclefindmkaj/ viewer.html?pdfurl=https%3A %2F%2Ftel.archives-ouvertes.fr %2Ftel-03169776%2Fdocument&clen=10841413 [retrieved on 2022-01-241; provided by Applicants) in further view of Secher et al (J. Controlled Release. Vol. 303, pages 24-33; provided by Applicants).
Karine et al relates to the use of mab166 in the treatment of respiratory ailments caused by P. aeruginosa (intratracheal (IT) administration).
However, Karine does not describe the combined administration of Mab166 and of CNCM 1-4967, CNCM-4968 or CNCMI-5314.
Geanncarlo et al relates to the identification of bacteria of the pulmonary microbiota which are capable of modifying the immune response during Mycobacterium tuberculosis infection. Among these bacteria, three are lactobacilli (L. salivarius, L. animalis and L. rhamnosus) which have a GRAS (Generally Recognised As Safe) organism status and have been deposited with the CNCM [French National Microorganism Culture Collection] under numbers: CNCM I 4968, CNCM I 5314 and CNCM I 4967, respectively. The three lactobacilli isolated from the pulmonary microbiota have strong immunomodulatory capacities, with an anti-inflammatory profile (even outside an infectious context). The use of an L. animalis strain (CNCM I-5314 is preferred) for use thereof in the treatment and/or prevention of inflammation related to a respiratory disease is claimed. The advantage of such a use compared to the use of antibiotics in the context, for example, of a P. aeruginosa infection is indicated.
Remot describes the isolation of Lactobacillaceae CNCM I 4967 and CNCM I 4968 from mouse lungs. The use of probiotics for pulmonary immunity in the treatment of pulmonary diseases is suggested.
Lucie et al describes the use of Lactobacillus murinus (CNCM I-5314) for reducing inflammation during Mycobacterium tuberculosis infection.
Secher shows that the administration of Mab166 directly into the airways confers more protection than parenteral administration, in the treatment of pneumonia caused by Pseudomonas aeruginosa.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to combine the Mab166 taught by both Karine and Secher with CNCM 1-4967, CNCM-4968 or CNCM-I-5314. It is known from Geancarllo, Remot and Lucie that the CNCM I-4967, CNCM I-4968 or CNCM-I-5314 strains have a beneficial effect in the treatment and/or prevention of inflammation related to a respiratory disease. Geancarllo clearly indicates that this is an advantageous alternative to antibiotics. The combination of two known treatments for the same disease is obvious to those of ordinary skill in the art. The fact that Mab166 and the CNCM 1-4967, CNCM-4968 or CNCM-I-5314 strains have been used in the treatment of one and the same pathological condition constitutes a suggestion for one of ordinary skill in the art to combine the agents in order to achieve a greater positive result.
With respect to Applicants’ arguments:
The term ‘immunostimulatory agent’ is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. A probiotic strain such as taught in the prior art references meets the structural limitations.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicants arguments that:
Applicant, however, disagrees with such assertion. Combining two treatments may have negative effects, for example, one treatment may cancel out the effects of the other one. Furthermore, choosing a particular combination is not necessarily obvious, since the effects of each treatment may not add up or may add up without synergy. The Applicant selected two specific treatments from a list of treatments for the same disease, not arbitrarily but because, as indicated by the test results given in the examples in the application, a beneficial and unexpected synergistic effect is obtained with the combination of these two treatments. Such a beneficial effect is illustrated in the application with the combination of mAb166+ immunostimulatory agent and now also in Appendix A with CN9114+ immunostimulatory agent.
These arguments re not commensurate in scope with the claimed invention.
Further, the Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Status of Claims:
No claims are presently allowed.
Pertinent art not presently relied upon:
Frank et al (WO 02/064161; provided by Applicants).
Frank et al describes a method for treating a respiratory infection caused by P. aeruginosa by means of the Mab166 antibody. See page 23 and claims 31-34. Combined administration with antibiotics is described. Preferably, human or humanized monoclonal or polyclonal antibodies to PcrV are administered to prevent or treat infections with P. aeruginosa. In patients at high risk for P. aeruginosa infection, antibodies could be administered for prevention of infection. In addition, antibodies may be administered after the onset of infection to treat the infection. In this case, antibodies can be administered alone or in combination with antibiotics.
Baer et al (WO 2010/091189; provided by Applicants).
Baer describes the combined use of an anti-PerV antibody (P. aeruginosa antagonist) and of an antibiotic for the treatment of a pulmonary infection caused by P. aeruginosa. See paragraph [0007]. The antibiotic may be administered by inhalation (see Para. 0103). Baer therefore describes the combination of an agent which is capable of binding an infectious agent and of at least one immunomodulatory agent. Para. [0009] The invention also provides a method of effectively enhancing the sensitivity of an antibiotic-resistant P. aeruginosa strain to the antibiotic when treating a subject infected with the strain, the method comprising administering to the subject the antibiotic and an anti-PerV antibody that is an antagonist of the P. aeruginosa TTSS. Para. [0010] The methods of the invention can be used to treat any subject having a P. aeruginosa infection, Often, the subject has cystic fibrosis, is on a mechanical ventilator, is a neutropenic cancer patient, or is a burn patient. The subject need not be human, but can also be an animal, such as a bovine, equine, ovine, porcine, canine, feline, primate, or any other animal. The methods of the invention for the combination treatment of a subject infected with P. aeruginosa can employ any antibody that neutralizes PerV, but in some embodiments use an anti-PerV antibody that competes with Mab166 for binding to PerV.
Lucie et al (J. Immunol. Sept. 2021. 207(7): 1857-1870; provided by applicants; after priority filing date).
Lucie et al (P-document) describes the use of the L. animalis strain (CNCM I-5314) for reducing inflammation in a tuberculosis model, by intranasal administration.
FINAL REJECTION
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.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached at (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 4/23/26
Prosecution Insights