DETAILED 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's claims filed on 07/22/2025 and the amended claim set filed on 10/24/2025 have been entered.
Amendments
Claim 1 has been amended to now require a composition comprising a first and second bacteriophage or a first and third bacteriophage and to require that the composition be formulated as an aerosol.
Claim 4 now requires the first, second, and third bacteriophages.
Claims 8-9, 14, 22, and 26 are canceled.
Claim 10 now requires at least 95% sequence identity to bacteriophages 1, 2, and 3.
Claim 23 now requires at least 90% sequence identity to bacteriophages 1, 2, and 3.
Examiner’s Note: It is noted that claim 23 is marked as “Previously Presented” and not “Currently Amended”. Because the claim contains mark-up, it is clear that applicant intended to amend this claim and the claim has therefore been examined as amended.
Claim 25 no longer recites suspensions.
Claim 27 has been amended to be an independent claim which recites the combination of bacteriophages with one or more stabilizers.
Claims 28-34 now depend from claim 27 and limit the composition of claim 27.
Claims 35-36 are newly added and limit the one or more stabilizers.
Election/Restrictions
Claims 1, 4-7, 10, 15-21, 23-25, and 27-36 are currently pending.
Claims 15-21 remain withdrawn as being directed to a non-elected invention.
Claims 1, 4-7, 10, 23-25, and 27-36 have been examined on their merits.
Claim Objections
Previous objections to the claims
Claims 1, 4, 14, and 24-25 were objected to for minor informalities. Applicant has made the appropriate corrections to claims 1, 4, and 24-25; therefore, the objection is withdrawn. Claim 14 is canceled, rendering the objection moot.
New objection to the claims
Claim 36 is objected to because a period is missing from the end of the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Previous rejection under 35 U.S.C. § 101
RE: Rejection of claims 1, 4-10, 12, 22-23, and 25 under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
Claims 1, 4-10, 12, 22-23, and 25 were rejected as being directed to a judicial exception without significantly more. Claims 1, 4-7, 10, and 23 now require the composition to be formulated for administration as an aerosol. Aerosols containing the judicial exceptions do not exist in nature and exhibit markedly different characteristics such as the small and well dispersed droplets containing the bacteriophages (see, for example, applicant’s remarks dated 10/18/2024 at p. 8-9).
For at least this reason, the rejection of claims 1, 4-7, 10, and 23 is withdrawn.
Claims 8-9, 12, and 22 are canceled, rendering their rejection moot.
Reasons for new grounds of rejection
Claim 27 has been amended to require a pharmaceutical composition comprising a pharmaceutically acceptable aqueous carrier, a therapeutically effective amount of a combination of purified bacteriophages, and one or more stabilizers.
The presence of a composition which is considered to be a “stabilizer” does not necessarily impart a markedly different characteristic. This term is broad and includes many compositions (see, e.g., claims 29-33) such as buffers, mannitol, nonionic surfactants, polysorbate, and NaCl. The specification provides further stabilizers including phosphate, citrate, other organic acids, antioxidants, low molecular weight polypeptides, proteins, hydrophilic polymers, amino acids, monosaccharides, disaccharides, other carbohydrates, chelating agents, sugar alcohols, salt-forming counter ions, and non-ionic surfactants. And although applicant’s argument with respect to the subject matter eligibility of the “Pomelo juice” example and the Kim et al. (Viruses, 2024, Vol. 16, Article 1155, pages 1-16) reference have been fully considered; the fact pattern of the instant claim is different for the following reasons.
The Pomelo juice claim required “an effective amount of an added preservative”. “Effective amount” was defined in the specification as an amount sufficient to prevent juice from spoiling for at least three weeks and indicates that suitable preservatives for fruit juices are known in the art. The instant claims do not require an “effective amount” of the stabilizer and therefore the claims allow for even a miniscule amount of “stabilizer”. There is no evidence that adding any amount of any stabilizer will cause the judicial exceptions to be markedly different in their stability. And to the extent that the prior art acknowledges the ability of certain compositions to “stabilize” bacteriophages, this is only with particular compositions and in particular amounts. Specifically, the Kim et al. reference cited by applicant teaches stabilizing phages with a combination of 0.1 M NaCl, 8 mM MgSO4▪7H2O, and 10% w/v D-Sorbitol (p. 4, section 2.6.2; p. 7, section 3.2) this is in stark contrast to the breadth of what is claimed in claim 27.
In summary, although certain compositions may “stabilize” the composition such that the composition, as a whole, exhibits a markedly different characteristic, merely adding a generic “stabilizer” is not sufficient to render the composition subject matter eligible, especially when it is not added in any particular amount which has been actually shown to promote stability to a markedly different extent.
For at least these reasons, claims 27-36 are not subject matter eligible and a new ground of rejection is set forth below.
Claims 27-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
The instant claims recites laws of nature and natural phenomena. These judicial exceptions (JEs) are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
The Markedly Different Characteristics Analysis
The first step in the analysis is to select the appropriate counterpart to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart. See MPEP § 2106.04(c)(II)(A).
The second step in the analysis is to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. Cf. Roslin, 750 F.3d at 1338, 110 USPQ2d at 1673. See MPEP § 2106.04(c)(II)(B). For this analysis, the ability to lyse K. pneumoniae or P. aeruginosa is an appropriate characteristic.
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. See MPEP § 2106.04(c)(II)(C).
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a);
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d);
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e) .
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step (1)(direction to a process, machine, manufacture, or composition of matter):
Claims 27-36 are directed to a composition of matter, which is a statutory category.
Therefore, the answer to this step for claims 27-36 is yes.
Step (2A), Prong 1 (recitation of a law of nature, natural phenomenon, or an abstract idea):
Claims 27-36 are directed to compositions comprising bacteriophages having at least 85% identity to bacteriophages which have been isolated from sewage water (i.e., from nature)([0116]). For the purpose of determining markedly different characteristics, the claimed bacteriophages’ closest natural counterpart are bacteriophages found in nature. There is no evidence in the specification that demonstrates that the combination of bacteriophages as claimed (i.e., 1/2, 1/3, or 1/2/3) have markedly different characteristics from naturally occurring bacteriophages.
Claim 27 further limits the therapeutically effective amount to 108 to 1011 plaque-forming units of each phage of the combination/ml of the pharmaceutical composition. Although, as discussed above, some concentrations of bacteriophages having 100% identity to SEQ ID NOs: 1 and 3 may elicit a markedly different (synergistic) characteristic, there is no evidence that every concentration encompassed by the claim elicits a markedly different characteristic, especially because the claims encompass bacteriophages having as little as 85% identity to these sequences.
Claim 27 further requires a pharmaceutically acceptable aqueous carrier. Pharmaceutically acceptable aqueous carriers are known in the art and include water, alcoholic/aqueous solutions, saline solutions, parenteral vehicles, Ringer’s dextrose, and the like (Yacoby et al., US 2008/0057038 A1; [0123]). There is no evidence that combining the bacteriophages with a composition such as water causes the composition to be markedly different in structure, property, or function.
Claim 27 further requires the composition to comprise one or more stabilizers. This term is not particularly limited and includes compositions such as phosphate, citrate, other organic acids, antioxidants, low molecular weight polypeptides, proteins, hydrophilic polymers, amino acids, monosaccharides, disaccharides, other carbohydrates, chelating agents, sugar alcohols, salt-forming counter ions, and non-ionic surfactants. There is no evidence that combining the bacteriophages with “one or more stabilizers” would cause the composition to be markedly different in structure, property, or function especially because the stabilizer is not particularly limited, nor is it required to actually be present in an amount which would elicit an improvement in bacteriophage stability.
For at least these reasons, claim 27 is directed to a composition which is not markedly different from the natural counterparts.
Claim 28 limits the composition to be a suspension and comprise a suspending agent. Suspensions include compositions such as the judicial exception in a naturally occurring medium such as water. There is no evidence that formulating the composition as a suspension would cause the composition to be markedly different in structure, property, or function. And although a suspending agent may elicit a markedly different characteristic (e.g., shelf stability), there is no evidence that such a characteristic exists and to the extent that a characteristic may exist, it is noted that the amount of suspending agent is not particularly limited. For example, a suspending agent such as a hydrocolloid may elicit a markedly different characteristic but such a characteristic may not exist when the composition comprises this component in a minuscule amount.
Claims 29-36 limit the composition to comprise certain stabilizers. As discussed above, the term stabilizer is broad and these claims, albeit limiting, are also broad. For example, claim 29 limits the stabilizer to a “buffer” and claim 35 limits the stabilizer to “an amino acid”. There is no evidence of record that adding any “stabilizer” such as a buffer or amino acid (in any amount) would elicit a markedly different characteristic. And to the extent that the compositions are limited to stabilizers such as “an amino acid”, it is noted that bacteriophages naturally possess “an amino acid” and therefore all compositions comprising bacteriophages also further comprise an amino acid.
For at least these reasons, the answer to this prong for claims 27-36 is yes.
Step (2A), Prong 2 (recitation of additional elements that integrate the JE into a practical application):
Claim 27 recites a pharmaceutically acceptable aqueous carrier. There is no evidence that inclusion of a pharmaceutically acceptable aqueous carrier integrates the judicial exceptions such as by transforming the judicial exceptions into a different state or thing.
Claim 27 further requires formulation in a therapeutically effective amount of 108 to 1011 PFU/ml. There is no evidence that formulation in these particular amounts effects a transformation or reduction the judicial exceptions to a different state or thing.
Claim 27 requires the composition to further comprise one or more stabilizers. As discussed above, the term stabilizers is not particularly limited and includes compositions such as phosphate, citrate, other organic acids, antioxidants, low molecular weight polypeptides, proteins, hydrophilic polymers, amino acids, monosaccharides, disaccharides, other carbohydrates, chelating agents, sugar alcohols, salt-forming counter ions, and non-ionic surfactants (Specification, [0067]). There is no evidence that combining the bacteriophages with “one or more stabilizers” (let alone every “stabilizer” in any amount) effects a transformation or reduction the judicial exceptions to a different state or thing.
Claim 28 limits the composition to be a suspension and comprise a suspending agent. Suspensions include compositions such as the judicial exception in a naturally occurring medium such as water. There is no evidence that formulating the composition as a suspension or including a suspending agent would effect a transformation or reduction the judicial exceptions to a different state or thing.
Claims 29-36 limit the composition to comprise certain stabilizers. As discussed above, the term stabilizer is broad and these claims, albeit limiting, are also broad. For example, claim 29 limits the stabilizer to a “buffer” and claim 35 limits the stabilizer to “an amino acid”. There is no evidence of record that adding any stabilizer such as a buffer or amino acid (in any amount) would effect a transformation or reduction the judicial exceptions to a different state or thing.
Therefore, the answer to this prong for claims 27-36 is no.
Step (2B)(recitation of additional elements that amount to significantly different than the JE such that they provide an inventive concept):
Claim 27 recites the composition comprising a “pharmaceutically acceptable aqueous carrier”. Coformulation of multiple bacteriophages with a “pharmaceutically acceptable aqueous carrier” is considered to be well-understood, routine, and conventional in the art. For example, Yacoby et al. (US 2008/0057038 A1) teaches bacteriophage-based compositions comprising pharmaceutically acceptable aqueous carriers such as water, alcoholic/aqueous solutions, saline solutions, parenteral vehicles, Ringer’s dextrose, and the like ([0122]-[0123]). Similarly, Côrte-Real (WO 2018/106135; cited previously) teaches pharmaceutical compositions comprising bacteriophages ([0115]-[0116]) which may be combined with compositions such as water ([0117]). As such, the coformulation of a bacteriophage with a generic pharmaceutically acceptable aqueous carrier does not provide an inventive concept.
Claim 27 further requires formulation in a therapeutically effective amount of 108 to 1011 PFU/ml. Both Chadha et al. (Microbial Pathogenesis, 2016, Vol. 99, p. 68-77; cited previously), and Côrte-Real teach formulation of bacteriophages in amounts falling within this range (Chadha, p. 70, “2.11. Phage efficacy studies”; Côrte-Real, [0219]). Thus, pharmaceutical compositions having this concentration are considered to be well-understood, routine, and conventional and are not considered to provide an inventive concept.
Claim 27 requires the composition to further comprise one or more stabilizers. As discussed above, the term stabilizers is not particularly limited and includes compositions such as phosphate, citrate, other organic acids, antioxidants, low molecular weight polypeptides, proteins, hydrophilic polymers, amino acids, monosaccharides, disaccharides, other carbohydrates, chelating agents, sugar alcohols, salt-forming counter ions, and non-ionic surfactants (Specification, [0067]). Côrte-Real teaches the coformulation of bacteriophages with stabilizers ([0116]). As such, the use of stabilizers is not considered to provide an inventive concept.
Claim 28 limits the composition to be a suspension and comprise a suspending agent. Suspensions include compositions such as the judicial exception in a naturally occurring medium such as water. Côrte-Real teaches the formulation of bacteriophages into a suspension ([0126], [0127], [0157]) and with a suspending agent ([0116]). As such, the formulation of the composition as a suspension with a suspending agent does not provide an inventive concept.
Claims 29-36 limit the composition to comprise a buffer (claims 29 and 34), mannitol (claims 30, 34, and 36), a nonionic surfactant (claim 31), polysorbate (claims 32 and 34), NaCl (claim 33), and an amino acid (claims 35-36). Côrte-Real teaches bacteriophage compositions comprising buffers, mannitol, nonionic surfactants, amino acids, polysorbates (TWEEN™) and NaCl ([0116] and [0192]). As such, the coformulation of bacteriophages with these components does not provide an inventive concept.
Therefore, the answer to step (2B) for claims 27-36 is no.
Conclusion
Claims 27-36 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
Allowable Subject Matter
Claims 1, 4-7, 10, and 23-24 are directed to pharmaceutical compositions comprising bacteriophages in an aerosolized state. Aerosolized bacteriophage compositions (1) do not occur in nature and (2) are markedly different in their dispersion characteristics when compared to naturally occurring bacteriophages. Accordingly, the claims directed to aerosolized bacteriophage compositions are subject matter eligible.
Claim 25 is directed to the pharmaceutical composition comprising a pharmaceutically acceptable carrier and purified bacteriophages wherein the carrier is an emulsion, cream, liposome, nanoparticle, and ointment. As discussed in the previous office action, Example 28 of the Life Sciences examples demonstrate that compositions which are emulsions, creams, liposomes, nanoparticles and ointments are subject matter eligible because they, like aerosols, provide markedly different characteristics on the compositions.
As discussed previously in prosecution, the prior art does not teach or suggest this specific combination of bacteriophages and the claims are therefore free of the art.
Conclusion
Claims 1, 4-7, 10, and 23-25 are allowable.
Claims 27-36 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GRANT C CURRENS whose telephone number is (571)272-0053. The examiner can normally be reached Monday - Thursday: 7:00-5:00.
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/GRANT C CURRENS/Examiner, Art Unit 1651