Referee 1: 
Minor points: 
-The headings "Results and Discussion 1/2/3..." seem inappropriate (and are there really results?) 

FOLLOWING ON FROM THE EXTENDED DESCRIPTION OF HOW THIS SUITE OF RELATIONS WAS ARRIVED AT, THE TERM ‘RESULTS’ HAS BEEN CONFINED TO THE SECTION PRESENTING THE LIST OF RELATIONS THEMSELVES
OTHER SECTIONS HAVE BEEN RELABELED CORRESPONDINGLY

-Page 9 "which out spatial relations" -> "which our spatial relations" 
FIXED

The cell ontology, reference [11], can be referenced more fully: An ontology for cell types. Bard, Rhee and Ashburner Genome Biology 2005, 6:R21 
http://genomebiology.com/2005/6/2/R21 

FIXED

Referee 3: 
First the minor issues: 
-On page 12 there is a close parenthesis without an open after "Note that C located_in C1 is an assertion about Cs in general" 
	-In the section "Continuants and Processes" the text starting with "Continuants are those entities which endure, or continue to exist,    through..." Might be moved to the beginning of the section so as to better introduce the terms before variables are named for them. 
	-In the discussion of is_a, "because it fails to take account of time, so that when applied to classes of continuants it yields    false positives such as adult is_a child;"  might be followed with a 

 short description of why that is so to help those readers who are 
not yet reasoning in the mode the paper proposes. Something like: 
"because every instance of adult was, at some time, an instance of child". 
-In the discussion of the derives_from the first example is "this fetus derives from this embryo". This seems to be an example of transformation_of. 

THE POINT IS WELL-TAKEN. THIS PASSAGE HAS BEEN CORRECTED

The authors explain that in general case a) is weaker than transformation_of by talking about *identity* of continuants, but it is not clear what is meant by identity. What might be better would be to choose an example that is in fact not a transformation_of so as to illuminate the distinction and give better insight on how the relation is to be applied. 
CONTRAST BETWEEN transformation AND derivation NOW MADE CLEARER ALONG THE LINES PROPOSED

- Youth and adulthood to illustrate processes and on the other hand child and adult as illustrate continuants. This brings attention to the fact that there might be two ways of describing the same thing - a process view and a classified continuant view - (a real issue when curating) but offers no advise as to what kinds of choices should be made in the choice of relations, and no logical connection between the two views. 
NEW PARAGRAPH ADDED, INCLUDING REFERENCE TO PUBLISHED WORK DESCRIBING THE LOGICAL RELATIONS BETWEEN THE TWO VIEWS

-In the table 2, listing the properties of the relations, contained_in is not listed as transitive. 
IT IS NOW MADE CLEARER THAT contained_in APPLIES ALWAYS ONLY BETWEEN A MATERIAL AND AN IMMATERIAL CONTINUANT (FOR EXAMPLE BETWEEN A PORTION OF BLOOD AND A CAVITY). ON THIS BASIS contained_in IS TRANSITIVE NEITHER ON THE INSTANCE NOR ON THE CLASS LEVEL
I wasn't sure if this was correct. If correct, it is worth mention since that is not the intuition one would have about containment - certainly the instance level relationship is transitive - and is worth calling attention to in the text. If incorrect, then it should be corrected. I did not check all of the entries in this table, however I had a similar question about derives_from being transitive. Perhaps these are of elementary enough nature that the table needs no further explanation, but it did occur to me that it might be of some pedagogic utility to include, as supplemental material, the proofs underlying the table. 
UNFORTUNATELY NOT ALL THE PROOFS ARE TRIVIAL. HOWEVER WE ARE PREPARING A SEPARATE PAPER CONTAINING FULL LOGICAL DETAILS (THIS PAPER IS SERVING ALSO AS A BASIS FOR THE CONSTRUCTION OF SOFTWARE FOR REASONING WITH DATA CODED IN TERMS OF THE RELATIONS HERE PRESENTED)

-It wasn't clear to me why derives_from, in particular, needed the extra machinery of provision for the cascade of derives_immediately_from relations. (as compared to, say, contained in)

THIS IS PERHAPS THE MOST DELICATE LOGICAL ISSUE IN THE WHOLE PAPER, AND AFTER MUCH WORK WE HAVE CONCLUDED THAT ALL DIRECT METHODS FOR DEFINING CLASS-LEVEL derivation FAIL BECAUSE THEY ALLOW TRIVIAL CASES (e.g. human derives_from human)

-In the discussion of the is_a relation the case of contingent inclusion is discussed as a criticism of of the initial formulation of the is_a relation but the reformulation doesn't rule it out. Although the author hints at an interesting direction in trying to formally clarify what appropriate biological class names might be, that discussion might be better placed in a discussion section of the paper so as not to interrupt the exposition. 
THE RELEVANT PASSAGE IS SHORTENED AND REFORMULATED TO FIT 
Larger issues: Has_agent relation 
This seems to me problematic from a number of points of view. 
-By definition only continuants can be agents, but in many cases biologists describe other processes as agents. An example, pulled from random from the literature: pubmed 12130701 "Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population." Here we have a process, hyperinsulinemia being described as an agent of an process of expression of an enzyme. Or consider the formation of chemotactic gradients in inflammation response, or diffusion in development and differentiation, or diabetes causing retinopathy. 
-Descriptions of metabolic reactions involved enzymes, cofactors, and metabolites. Which is the agent? In protein degradation via the proteasome, proteins are tagged with ubiquitin by a ubiquitin ligase and such proteins are targeted by the proteasome for degradation. Which is the agent of degradation? The proteasome, ubiquitin, ligase. There are some interesting cases in the database I manage where over time interactions which are first described in the literature as causing degradation are, in later papers, described as effecting ubuqination. 
-Processes typically have more nuanced descriptions of the roles of    the participants. For instance, acceptor and donor, or scaffolding    proteins involved in other interactions. When the need for these arises, how will these new relations interact with curation which previously used has_agent? 
-The use of agent slot and similar has had a bad effect on our ability    to classify interactions as direct physical vs indirect interactions because it makes no such distinction and this distinction is important in computational methods, for instance it is a topic of current debate in the BioPax discussion list. 
ALL OF THE ABOVE HAVE BEEN ADDRESSED IN WHAT WE HOPE IS A CLARIFIED TREATMENT OF has_agent THAT IS DESIGNED TO ENSURE THAT CARE IS TAKEN IN THE USE OF THIS RELATION IN CURATION IN WAYS WHICH WILL HELP TO WARD OFF THE PROBLEMS MENTIONED

The relation part-of used for both processes and continuants. 
-I think inferences which involve propogation across parts will function differently depending on whether the relation is between processes or continuants. The meaning of part-of in these cases is sufficiently different that coding errors and inference is likely to more error prone. The part-of relation is the only one of the lot that allows a position in the relation to be occupied by either a continuant or a process. 
A CLARIFICATORY REMARK HAS BEEN ADDED AT THE END OF THE SECTION INTRODUCING part_of TO FIX THE INFERENCE PROBLEM. AS TO CODING ERRORS, SEE BELOW.

Theory of types and composition of relations. 
-There is some theory of types, in the sense that relations specify 
 what type of things are allowed to be related by the relation. Three 
types are mentioned: Material continuants, immaterial continuants 
and processes. Is this adequate? Although the paper focuses on 
relations, this seems to be a constraint on the top levels of the 
   ontologies. Is such a constraint enforced in the OBO ontologies? 
ONLY THREE TYPES OF BIOLOGICAL ENTITIES ARE DISTINGUISHED HERE (TOGETHER WITH TEMPORAL INSTANTS AND SPATIAL REGIONS). IN AN EXPANDED VERSION IT WOULD BE NECESSARY ALSO WITH ATTRIBUTES, VALUES, FUNCTIONS AND OTHER DEPENDENT CONTINUANTS (INCLUDING DISORDERS SUCH AS DIABETES, WHICH ARE TO BE DISTINGUISHED FROM THE CORRESPONDING COURSES OR HISTORIES, WHICH ARE PROCESSES)
WE HAVE ADVERTED, BRIEFLY, TO ALL OF THE ABOVE AT CRUCIAL POINTS IN THE TEXT, BUT HAVE NOT PURSUED ANY OF THEM IN ANY DETAIL IN ORDER NOT TO OVERTAX THE READER. OUR EXPERIMENTS HAVE SHOWN, HOWEVER, THAT WHEN CURATORS ARE PROVIDED WITH AN ONTOLOGY WHICH MAKES CLEAR THE DISTINCTIONS BETWEEN INDEPENDENT CONTINUANTS (TREATED IN THIS PAPER), DEPENDENT CONTINUANTS AND PROCESSES, THEN MANY OF THE COMMON TYPES OF ERRORS ARE AVOIDED. (SEE E.G. THE DISCUSSION HERE:
dos Santos MC, Dhaen C, Fielding M, Ceusters W: Philosophical Scrutiny for Run-Time Support of Application Ontology Development, in: Proceedings of FOIS 2004 (Formal Ontology and Information Systems), 342-352.  http://ontology.buffalo.edu/medo/Run-Time-Support.pdf

-How do the various relations interact with each other. Simple examples are does has_agent imply has_participant? More complicated ones are things like whether a participant of a subprocess is also considered a participant in the process which the subprocess is a part-of. 

IN THE LOGICAL PAPER REFERRED TO ABOVE WE PROVIDE A COMPLETE SET OF AXIOMS GOVERNING SUCH INTERACTIONS